47 CFR 73.210 - Station classes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... this distance is greater than 39 km and less than or equal to 52 km, the station is Class B. (3) For a... than or equal to 78 km, the station is Class B. [52 FR 37788, Oct. 9, 1987; 52 FR 39920, Oct. 26, 1987.... Class A, B1 and B stations may be authorized in Zones I and I-A. Class A, C3, C2, C1, C0 and C stations...

47 CFR 73.210 - Station classes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... this distance is greater than 39 km and less than or equal to 52 km, the station is Class B. (3) For a... than or equal to 78 km, the station is Class B. [52 FR 37788, Oct. 9, 1987; 52 FR 39920, Oct. 26, 1987.... Class A, B1 and B stations may be authorized in Zones I and I-A. Class A, C3, C2, C1, C0 and C stations...

47 CFR 73.210 - Station classes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... this distance is greater than 39 km and less than or equal to 52 km, the station is Class B. (3) For a... than or equal to 78 km, the station is Class B. [52 FR 37788, Oct. 9, 1987; 52 FR 39920, Oct. 26, 1987.... Class A, B1 and B stations may be authorized in Zones I and I-A. Class A, C3, C2, C1, C0 and C stations...

25 CFR 535.1 - Amendments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR MANAGEMENT CONTRACT PROVISIONS POST-APPROVAL PROCEDURES... management contract for the operation of a class II or class III gaming activity. (b) A tribe shall submit an... information required under § 537.1(b)(1) of this chapter for class II gaming contracts or § 537.1(b)(1)(i) of...

HLA class-I and class-II allele frequencies and two-locus haplotypes in Melanesians of Vanuatu and New Caledonia.

PubMed

Maitland, K; Bunce, M; Harding, R M; Barnardo, M C N M; Clegg, J B; Welsh, K; Bowden, D K; Williams, T N

2004-12-01

HLA class-I and class-II allele frequencies and two-locus haplotypes were examined in 367 unrelated Melanesians living on the islands of Vanuatu and New Caledonia. Diversity at all HLA class-I and class-II loci was relatively limited. In class-I loci, three HLA-A allelic groups (HLA-A*24, HLA-A*34 and HLA-A*11), seven HLA-B alleles or allelic groups (HLA-B*1506, HLA-B*5602, HLA-B*13, HLA-B*5601, HLA-B*4001, HLA-B*4002 and HLA-B*2704) and four HLA-C alleles or allelic groups (HLA-Cw*04, HLA-Cw*01, HLA-Cw*0702 and HLA-Cw*15) constituted more than 90% of the alleles observed. In the class-II loci, four HLA-DRB1 alleles (HLA-DRB1*15, HLA-DRB1*11, HLA-DRB1*04 and HLA-DRB1*16), three HLA-DRB3-5 alleles (HLA-DRB3*02, HLA-DRB4*01 and HLA-DRB5*01/02) and five HLA-DQB1 alleles (HLA-DQB1*0301, HLA-DQB1*04, HLA-DQB1*05, HLA-DQB1*0601 and HLA-DQB1*0602) constituted over 93, 97 and 98% of the alleles observed, respectively. Homozygosity showed significant departures from expected levels for neutrality based on allele frequency (i.e. excess diversity) at the HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB3/5 loci on some islands. The locus with the strongest departure from neutrality was HLA-DQB1, homozygosity being significantly lower than expected on all islands except New Caledonia. No consistent pattern was demonstrated for any HLA locus in relation to malaria endemicity.

"What's in a structure?" The story of biguanides

NASA Astrophysics Data System (ADS)

Kathuria, Deepika; Bankar, Apoorva A.; Bharatam, Prasad V.

2018-01-01

Biguanides are a very interesting class of molecules which have been extensively studied for their medicinal applications. The structural and electronic structural aspects of biguanides have been explored in detail; however, even today, scientific literature continues to represent biguanides incorrectly as 1a. The X-ray crystal structure analysis and various spectroscopic studies such as UV, 1H and 15N NMR have confirmed that biguanide exists as tautomer 1b. Electronic structure analysis also supports the existence of 1b. This review focuses on the structure and electronic structure of biguanides and aims to emphasize the importance of the correct representation of a structure. There is a need to commence the use of 1b for the general representation of biguanides in textbooks and research articles which will ensure a correct perspective for further studies on these molecules.

Dibenzosiloles and 12H-indololo[3,2-d]naphtho[1,2-b][1]siloles: exploration of organic chromophores exhibiting efficient solid-state fluorescence.

PubMed

Shimizu, Masaki

2015-02-01

The construction of a diorganosilylene bridge over a biaryl moiety at the 2,2'-positions is a versatile strategy for fine-tuning its HOMO-LUMO energy gap, which is closely linked to the electronic and optical properties of the compounds. Therefore, there is growing interest in the use of silicon-bridged biaryl motifs as key cores of various types of advanced functional materials, such as light-emitting, semiconducting, photovoltaic, and sensing materials. To accelerate the advances of materials based on silicon-bridged biaryls, it is essential to create new classes of biaryls and explore their functions and properties. This Personal Account describes recent research on the development of organic chromophores based on functionalized dibenzosiloles and 12H-indololo[3,2-d]naphtho[1,2-b][1]siloles as solid-state emitters. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

American Society of Anesthesiologists classification in cataract surgery: Results from the Ophthalmic Surgery Outcomes Data Project.

PubMed

Payal, Abhishek R; Sola-Del Valle, David; Gonzalez-Gonzalez, Luis A; Cakiner-Egilmez, Tulay; Chomsky, Amy S; Vollman, David E; Baze, Elizabeth F; Lawrence, Mary; Daly, Mary K

2016-07-01

To explore the association of American Society of Anesthesiologists (ASA) classification with cataract surgery outcomes. Five Veterans Affairs Medical Centers, United States. Retrospective observational cohort study. The study analyzed the outcomes of cataract surgery cases. Corrected distance visual acuity (CDVA), unanticipated events, and vision-related quality of life (VRQL) were assessed using the National Eye Institute Visual Function Questionnaire (NEI-VFQ), comparing ASA classes I through IV. For some analyses, ASA classes I and II were designated as Group A and ASA classes III and IV were designated Group B. Of the 4923 cases, 875 (17.8%) were in Group A, 4032 (81.9%) were in Group B, and 16 (0.3%) had missing data. The mean CDVA and mean composite NEI-VFQ score improved after cataract surgery in both groups (P < .0001); however, Group A had a better mean postoperative CDVA and postoperative VFQ composite scores than Group B (P < .0001, both outcomes). A higher ASA class was associated with an increased risk for 2 unanticipated events; that is, clinically significant macular edema (CSME) (Group A: 4 [0.47%] versus Group B: 50 [1.28%]; adjusted odds ratio [OR], 3.02; 95% confidence interval [CI], 1.02-13.05; P = 0.04) and readmission to the hospital within 30 days (2 [0.23%] versus 56 [1.41%]; OR, 8.26; 95% CI, 1.71-148.62; P = .004) CONCLUSIONS: Among United States veterans, the ASA classification could be an important predictor of VRQL and visual outcomes. In this cohort, it was associated with an increased risk for 2 serious unanticipated events-CSME and readmission to the hospital-both costly, unwanted outcomes. Dr. Vollman is a consultant to Forsight Vision5. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Contextual control using a go/no-go procedure with compound abstract stimuli.

PubMed

Modenesi, Rafael Diego; Debert, Paula

2015-05-01

Contextual control has been described as (1) a five-term contingency, in which the contextual stimulus exerts conditional control over conditional discriminations, and (2) allowing one stimulus to be a member of different equivalence classes without merging them into one. Matching-to-sample is the most commonly employed procedure to produce and study contextual control. The present study evaluated whether the go/no-go procedure with compound stimuli produces equivalence classes that share stimuli. This procedure does not allow the identification of specific stimulus functions (e.g., contextual, conditional, or discriminative functions). If equivalence classes were established with this procedure, then only the latter part of the contextual control definition (2) would be met. Six undergraduate students participated in the present study. In the training phases, responses to AC, BD, and XY compounds with stimuli from the same classes were reinforced, and responses to AC, BD, and XY compounds with stimuli from different classes were not. In addition, responses to X1A1B1, X1A2B2, X2A1B2, and X2A2B1 compounds were reinforced and responses to the other combinations were not. During the tests, the participants had to respond to new combinations of stimuli compounds YCD to indicate the formation of four equivalence classes that share stimuli: X1A1B1Y1C1D1, X1A2B2Y1C2D2, X2A1B2Y2C1D2, and X2A2B1Y2C2D1. Four of the six participants showed the establishment of these classes. These results indicate that establishing contextual stimulus functions is unnecessary to produce equivalence classes that share stimuli. Therefore, these results are inconsistent with the first part of the definition of contextual control. © Society for the Experimental Analysis of Behavior.

14 CFR 61.95 - Operations in Class B airspace and at airports located within Class B airspace.

Code of Federal Regulations, 2010 CFR

2010-01-01

... unless: (1) The student pilot has received both ground and flight training from an authorized instructor on that Class B airspace area, and the flight training was received in the specific Class B airspace... the authorized instructor who gave the student pilot flight training, and the endorsement is dated...

14 CFR 61.95 - Operations in Class B airspace and at airports located within Class B airspace.

Code of Federal Regulations, 2011 CFR

2011-01-01

... unless: (1) The student pilot has received both ground and flight training from an authorized instructor on that Class B airspace area, and the flight training was received in the specific Class B airspace... the authorized instructor who gave the student pilot flight training, and the endorsement is dated...

The NASA Human Research Wiki - An Online Collaboration Tool

NASA Technical Reports Server (NTRS)

Barr, Yael; Rasbury, Jack; Johnson, Jordan; Barstend, Kristina; Saile, Lynn; Watkins, Sharmi

2012-01-01

The Exploration Medical Capability (ExMC) element is one of six elements of the Human Research Program (HRP). ExMC is charged with decreasing the risk of: "Inability to adequately recognize or treat an ill or injured crew member" for exploration-class missions In preparation for exploration-class missions, ExMC has compiled a large evidence base, previously available only to persons within the NASA community. ExMC has developed the "NASA Human Research Wiki" in an effort to make the ExMC information available to the general public and increase collaboration within and outside of NASA. The ExMC evidence base is comprised of several types of data, including: (1)Information on more than 80 medical conditions which could occur during space flight (a)Derived from several sources (b)Including data on incidence and potential outcomes, as captured in the Integrated Medical Model s (IMM) Clinical Finding Forms (CliFFs). (2)Approximately 25 gap reports (a)Identify any "gaps" in knowledge and/or technology that would need to be addressed in order to provide adequate medical support for these novel missions.

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to... achieved: (1) The ERP and antenna HAAT of the proposed station in the direction of the contours of other...

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to... achieved: (1) The ERP and antenna HAAT of the proposed station in the direction of the contours of other...

Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

PubMed Central

Lakraj, Amanda-Amrita D.; Moghimi, Narges; Jabbari, Bahman

2013-01-01

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent. PMID:23612753

HLA class I and class II haplotypes in admixed families from several regions of Mexico.

PubMed

Barquera, Rodrigo; Zúñiga, Joaquín; Hernández-Díaz, Raquel; Acuña-Alonzo, Victor; Montoya-Gama, Karla; Moscoso, Juan; Torres-García, Diana; García-Salas, Claudia; Silva, Beatriz; Cruz-Robles, David; Arnaiz-Villena, Antonio; Vargas-Alarcón, Gilberto; Granados, Julio

2008-02-01

We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA-A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies.

Identification of a Fungal 1,8-Cineole Synthase from Hypoxylon sp. with Specificity Determinants in Common with the Plant Synthases*

PubMed Central

Shaw, Jeffrey J.; Berbasova, Tetyana; Sasaki, Tomoaki; Jefferson-George, Kyra; Spakowicz, Daniel J.; Dunican, Brian F.; Portero, Carolina E.; Narváez-Trujillo, Alexandra; Strobel, Scott A.

2015-01-01

Terpenes are an important and diverse class of secondary metabolites widely produced by fungi. Volatile compound screening of a fungal endophyte collection revealed a number of isolates in the family Xylariaceae, producing a series of terpene molecules, including 1,8-cineole. This compound is a commercially important component of eucalyptus oil used in pharmaceutical applications and has been explored as a potential biofuel additive. The genes that produce terpene molecules, such as 1,8-cineole, have been little explored in fungi, providing an opportunity to explore the biosynthetic origin of these compounds. Through genome sequencing of cineole-producing isolate E7406B, we were able to identify 11 new terpene synthase genes. Expressing a subset of these genes in Escherichia coli allowed identification of the hyp3 gene, responsible for 1,8-cineole biosynthesis, the first monoterpene synthase discovered in fungi. In a striking example of convergent evolution, mutational analysis of this terpene synthase revealed an active site asparagine critical for water capture and specificity during cineole synthesis, the same mechanism used in an unrelated plant homologue. These studies have provided insight into the evolutionary relationship of fungal terpene synthases to those in plants and bacteria and further established fungi as a relatively untapped source of this important and diverse class of compounds. PMID:25648891

Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

PubMed

Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z

2016-05-01

Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.

TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling

PubMed Central

Jin, Jin; Xiao, Yichuan; Chang, Jae-Hoon; Yu, Jiayi; Hu, Hongbo; Starr, Robyn; Brittain, George C.; Chang, Mikyoung; Cheng, Xuhong; Sun, Shao-Cong

2012-01-01

Immunoglobulin (Ig) class switching is crucial for generating antibody diversity in humoral immunity and, if deregulated, also has severe pathological consequences. How the magnitude of Ig isotype switching is controlled is still poorly understood. Here we identify TANK-binding kinase 1 (TBK1) as a pivotal negative regulator of IgA class switching. B cell-specific TBK1 ablation in mice resulted in uncontrolled production of IgA and development of nephropathy-like disease symptoms. TBK1 negatively regulated IgA class switching by attenuating noncanonical NF-κB signaling, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase. These findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and highlight a unique mechanism that controls IgA production. PMID:23023393

Characterization and Functional Analysis of Five MADS-Box B Class Genes Related to Floral Organ Identification in Tagetes erecta.

PubMed

Ai, Ye; Zhang, Chunling; Sun, Yalin; Wang, Weining; He, Yanhong; Bao, Manzhu

2017-01-01

According to the floral organ development ABC model, B class genes specify petal and stamen identification. In order to study the function of B class genes in flower development of Tagetes erecta, five MADS-box B class genes were identified and their expression and putative functions were studied. Sequence comparisons and phylogenetic analyses indicated that there were one PI-like gene-TePI, two euAP3-like genes-TeAP3-1 and TeAP3-2, and two TM6-like genes-TeTM6-1 and TeTM6-2 in T. erecta. Strong expression levels of these genes were detected in stamens of the disk florets, but little or no expression was detected in bracts, receptacles or vegetative organs. Yeast hybrid experiments of the B class proteins showed that TePI protein could form a homodimer and heterodimers with all the other four B class proteins TeAP3-1, TeAP3-2, TeTM6-1 and TeTM6-2. No homodimer or interaction was observed between the euAP3 and TM6 clade members. Over-expression of five B class genes of T. erecta in Nicotiana rotundifolia showed that only the transgenic plants of 35S::TePI showed altered floral morphology compared with the non-transgenic line. This study could contribute to the understanding of the function of B class genes in flower development of T. erecta, and provide a theoretical basis for further research to change floral organ structures and create new materials for plant breeding.

47 CFR 15.101 - Equipment authorization of unintentional radiators.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... TV interface device Declaration of Conformity or Certification. Cable system terminal device Declaration of Conformity. Stand-alone cable input selector switch Verification. Class B personal computers... used with Class B personal computers Declaration of Conformity or Certification. 1 Class B personal...

47 CFR 15.101 - Equipment authorization of unintentional radiators.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... TV interface device Declaration of Conformity or Certification. Cable system terminal device Declaration of Conformity. Stand-alone cable input selector switch Verification. Class B personal computers... used with Class B personal computers Declaration of Conformity or Certification. 1 Class B personal...

47 CFR 15.101 - Equipment authorization of unintentional radiators.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... TV interface device Declaration of Conformity or Certification. Cable system terminal device Declaration of Conformity. Stand-alone cable input selector switch Verification. Class B personal computers... used with Class B personal computers Declaration of Conformity or Certification. 1 Class B personal...

47 CFR 15.101 - Equipment authorization of unintentional radiators.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... TV interface device Declaration of Conformity or Certification. Cable system terminal device Declaration of Conformity. Stand-alone cable input selector switch Verification. Class B personal computers... used with Class B personal computers Declaration of Conformity or Certification. 1 Class B personal...

47 CFR 15.101 - Equipment authorization of unintentional radiators.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... TV interface device Declaration of Conformity or Certification. Cable system terminal device Declaration of Conformity. Stand-alone cable input selector switch Verification. Class B personal computers... used with Class B personal computers Declaration of Conformity or Certification. 1 Class B personal...

26 CFR 1.305-4 - Distributions of common and preferred stock.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of common stock, class A and class B. Dividends may be paid in stock or in cash on either class of stock without regard to the medium of payment of dividends on the other class. A dividend is declared on the class A stock payable in additional shares of class A stock and a dividend is declared on class B...

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

PubMed Central

Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

2016-01-01

Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to...) C3 to C1 200 (124) 133 (83) 70 (43) C3to C0 215 (134) 152 (94) 81 (50) C3 to C 226 (140) 165 (103) 90...

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to...) C3 to C1 200 (124) 133 (83) 70 (43) C3to C0 215 (134) 152 (94) 81 (50) C3 to C 226 (140) 165 (103) 90...

A Children's Oncology Group and TARGET Initiative Exploring the Genetic Landscape of Wilms Tumor

PubMed Central

Gadd, Samantha; Huff, Vicki; Walz, Amy L.; Ooms, Ariadne H.A.G.; Armstrong, Amy E.; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C.; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Dome, Jeffrey S.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Ross, Nicole; Gastier-Foster, Julie M.; Arold, Stefan T.; Perlman, Elizabeth J.

2017-01-01

Genome-wide sequencing, mRNA and miRNA expression, DNA copy number and methylation analyses were performed on 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, FAM123B, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), mutations were identified in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and let-7a loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development. PMID:28825729

High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

PubMed Central

Liu, Yanhou; Zhao, Zhongfang; Li, Tianyi; Liao, Qi; Kushner, Nicholas; Touzjian, Neal Y.; Shao, Yiming; Sun, Yongtao; Strong, Amie J.; Lu, Yichen

2012-01-01

Background Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort. Methodology/Principal Findings Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group. Conclusions At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates. PMID:23251376

Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization.

PubMed

An, Xiao-De; Liu, Hongyan; Xu, Zhong-Liang; Jin, Yi; Peng, Xia; Yao, Ying-Ming; Geng, Meiyu; Long, Ya-Qiu

2015-02-01

Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two imidazonaphthyridinone frameworks with 1,8- and 3,5-disubstitution pattern as class I and class II c-Met kinase inhibitors, respectively. Further structural optimization on type II inhibitors by truncation of the imidazonaphthyridinone core and incorporation of an N-phenyl cyclopropane-1,1-dicarboxamide pharmacophore led to the discovery of novel imidazopyridine-based c-Met kinase inhibitors, displaying nanomolar enzyme inhibitory activity and improved Met kinase selectivity. More significantly, the new chemotype c-Met kinase inhibitors effectively inhibited Met phosphorylation and its downstream signaling as well as the proliferation of Met-dependent EBC-1 human lung cancer cells at submicromolar concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site

PubMed Central

West, Anthony P; Schamber, Michael; Gazumyan, Anna; Golijanin, Jovana; Seaman, Michael S; Fätkenheuer, Gerd; Klein, Florian; Nussenzweig, Michel C; Bjorkman, Pamela J

2016-01-01

HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-Å- and 3.9-Å-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46–derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs. PMID:27617431

33 CFR 67.25-1 - Class “B” structures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Class âBâ structures. 67.25-1... NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Class âBâ Requirements § 67.25-1 Class “B” structures. Class “B” structures shall be the structures erected in an area where Class “B...

A data-driven approach for the study of coagulation phenomena in waste lubricant oils and its relevance in alkaline regeneration treatments.

PubMed

Pinheiro, C T; Ascensão, V R; Reis, M S; Quina, M J; Gando-Ferreira, L M

2017-12-01

Coagulation phenomena can occur in certain types of waste lubricant oils (WLO) during regeneration processes involving alkaline treatments, causing plant shutdowns. In this context, this study addresses the nature of the compounds responsible for the coagulation phenomena after the alkaline treatment. For such, an empirical test was developed to assess the coagulation behaviour of WLO, consisting in the addition of KOH to the WLO followed by heating under stirring conditions. This test was performed on 133 samples and four coagulation classes were identified: A; B1; B2 and C. Moreover, a physicochemical characterization of WLO was carried out regarding viscosity at 40°C, saponification number (SN), total acid number (TAN), surface tension, water content, elemental analysis and functional groups (FTIR). 56 samples of fresh lubricant oils for different applications were also characterized and their properties assessed and compared. Multivariate methods were applied to WLO to discriminate among coagulation classes based on FTIR spectra. It was found that coagulation classes A and B1 exhibit statistically similar patterns for all properties determined. Spectral discriminating analysis did not reveal discriminant peaks for class B1 samples, and the presence of specific additives was pointed as the possible factor underlying the increase in viscosity in this oils. Class B2 presents the absence of additives and oxidation products as differentiating features. In addition, B2 samples showed lower TAN SN, and lower concentration of some elements. Lubricants from gear or hydraulic applications can give rise to this class of WLO. Oils of Class C are mainly composed by synthetic ester type base oils, which hamper regeneration processes using alkaline pretreatments. In future studies, WLO type A and B1 can be classified as a single class. The coagulation phenomena classification becomes A - negative, B - precipitate formation and C - positive. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of social class in the formation of identity: a study of public and elite private college students.

PubMed

Aries, Elizabeth; Seider, Maynard

2007-04-01

The authors explored the influence of social class on identity formation in an interview study of 15 lower income students and 15 affluent students from a highly selective liberal arts school and 15 lower income students from a state college. Students ranked occupational goals as 1st in importance to identity and social class as 2nd. The affluent students regarded social class as significantly more important to identity than did the lower income students, were more aware of structural factors contributing to their success, and had higher occupational aspirations. Social class was an area of exploration for half the students, with higher levels of exploration shown by the lower income private school students than by the state college students. Lower income students developed an ideology that rationalized their social class position.

Comparative expression profiling of AtRAD5B and AtNDL1: Hints towards a role in G protein mediated signaling.

PubMed

Khatri, Nisha; Singh, Swati; Hakim, Nasmeen; Mudgil, Yashwanti

2017-11-01

Arabidopsis AtRAD5B encodes for a putative helicase of the class SWItch/Sucrose Non-Fermentable (SWI/SNF) ATPases. We identified AtRAD5B as an interactor of N-MYC DOWNREGULATED-LIKE1 (AtNDL1) in a yeast two-hybrid screen. AtNDL1 is a G protein signaling component which regulates auxin transport and gradients together with GTP binding protein beta 1 (AGB1). Auxin gradients are known to recruit SWI/SNF remodeling complexes to the chromatin and regulate expression of genes involved in flower and leaf formation. In current study, a comparative spatial and temporal co-expression/localization analysis of AtNDL1, AGB1 with AtRAD5B was carried out in order to explore the possibility of their coexistence in a common signaling network. Translational fusion (GUS) of AtNDL1 and AtRAD5B in seedlings and reproductive organs revealed that both shared similar expression patterns with the highest expression observed in male reproductive organs. Moreover, they shared similar domains of localization in roots, suggesting their potential functioning together in reproductive and root development processes. This study predicts the existence of a signaling network involving AtNDL1, AGB1 with AtRAD5B. Copyright © 2017 Elsevier B.V. All rights reserved.

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. – NASA astronaut candidate Tyler "Nick" Hague surveys the flame trench at Launch Complex 39B at NASA's Kennedy Space Center during a daylong set of briefings and tours of different facilities at NASA's primary launch center. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

PubMed Central

Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

2015-01-01

Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

26 CFR 1.305-1 - Stock dividends.

Code of Federal Regulations, 2010 CFR

2010-04-01

... exchange for its convertible preferred class B stock. Under the terms of the class B stock, its conversion... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Stock dividends. 1.305-1 Section 1.305-1...) INCOME TAXES Effects on Recipients § 1.305-1 Stock dividends. (a) In general. Under section 305, a...

47 CFR 36.212 - Basic local services revenue-Account 5000 (Class B telephone companies); Basic area revenue...

Code of Federal Regulations, 2010 CFR

2010-10-01

... (Class B telephone companies); Basic area revenue-Account 5001 (Class A telephone companies). 36.212..., REVENUES, EXPENSES, TAXES AND RESERVES FOR TELECOMMUNICATIONS COMPANIES 1 Operating Revenues and Certain... companies); Basic area revenue—Account 5001 (Class A telephone companies). (a) Local private line revenues...

An Investigation of Language Teachers' Explorations of the Use of Corpus Tools in the English for Academic Purposes (EAP) Class

ERIC Educational Resources Information Center

Bunting, John David

2013-01-01

Despite claims that the use of corpus tools can have a major impact in language classrooms (e.g., Conrad, 2000, 2004; Davies, 2004; O'Keefe, McCarthy, & Carter, 2007; Sinclair, 2004b; Tsui, 2004), many language teachers express apparent apathy or even resistance towards adding corpus tools to their repertoire (Cortes, 2013b). This study…

Identification, characterization, and quantitation of soluble HLA antigens in the circulation and peritoneal dialysate of renal patients.

PubMed Central

Gelder, F B; McDonald, J C; Landreneau, M D; McMillan, R M; Aultman, D F

1991-01-01

Human lymphocyte antigen (HLA) class I and class II antigens and beta 2 microglobulin (B2M) were identified in peritoneal dialysate (PD) and serum from patients with end-stage renal disease (ESRD) using monoclonal antibodies in an enzyme-linked immunoassay. The HLA class I and class II antigens each exhibited approximate molecular weights of 50,000 to 60,000 daltons by chromatography on Sepharose CL 6B. Class I antigens in serum and PD fluid were associated with B2M. Free B2M (Mr 11,500) also was detected in both sera and PD fluids. Unlike class I antigens, class II antigens were not found to have attached B2M. Class I and class II antigens eluted from 2-diethylaminoethanol ion exchange gradient columns at 0.07 mol/L (molar) phosphate buffer pH 7.2 and migrated with alpha 2-beta 1 mobility in agarose electrophoresis. Class I antigens were purified from ESRD patients' PD fluid by solid-phase immunoaffinity chromatography. Enzyme-linked immunoassay demonstrated that this purified protein was composed of a class I heavy chain and B2M. Class I allospecificity was confirmed by neutralization on known HLA typing antisera in a microcytotoxicity assay. Soluble HLA class I antigen preparations specifically inhibited blast transformation of responder lymphocytes in mixed lymphocyte culture reactions. Inhibition was dose dependent and ranged from 0% to 95%. The presence of soluble HLA antigens in body fluids may play an important part in the immunologic tolerance to self. This study demonstrates a ready source of large quantities of soluble HLA for detailed analysis. Images Fig. 1. PMID:2039290

New class of two-loop neutrino mass models with distinguishable phenomenology

NASA Astrophysics Data System (ADS)

Cao, Qing-Hong; Chen, Shao-Long; Ma, Ernest; Yan, Bin; Zhang, Dong-Ming

2018-04-01

We discuss a new class of neutrino mass models generated in two loops, and explore specifically three new physics scenarios: (A) doubly charged scalar, (B) dark matter, and (C) leptoquark and diquark, which are verifiable at the 14 TeV LHC Run-II. We point out how the different Higgs insertions will distinguish our two-loop topology with others if the new particles in the loop are in the simplest representations of the SM gauge group.

PEG Enhancement for EM1 and EM2+ Missions

NASA Technical Reports Server (NTRS)

Von der Porten, Paul; Ahmad, Naeem; Hawkins, Matt

2018-01-01

NASA is currently building the Space Launch System (SLS) Block-1 launch vehicle for the Exploration Mission 1 (EM-1) test flight. The next evolution of SLS, the Block-1B Exploration Mission 2 (EM-2), is currently being designed. The Block-1 and Block-1B vehicles will use the Powered Explicit Guidance (PEG) algorithm. Due to the relatively low thrust-to-weight ratio of the Exploration Upper Stage (EUS), certain enhancements to the Block-1 PEG algorithm are needed to perform Block-1B missions. In order to accommodate mission design for EM-2 and beyond, PEG has been significantly improved since its use on the Space Shuttle program. The current version of PEG has the ability to switch to different targets during Core Stage (CS) or EUS flight, and can automatically reconfigure for a single Engine Out (EO) scenario, loss of communication with the Launch Abort System (LAS), and Inertial Navigation System (INS) failure. The Thrust Factor (TF) algorithm uses measured state information in addition to a priori parameters, providing PEG with an improved estimate of propulsion information. This provides robustness against unknown or undetected engine failures. A loft parameter input allows LAS jettison while maximizing payload mass. The current PEG algorithm is now able to handle various classes of missions with burn arcs much longer than were seen in the shuttle program. These missions include targeting a circular LEO orbit with a low-thrust, long-burn-duration upper stage, targeting a highly eccentric Trans-Lunar Injection (TLI) orbit, targeting a disposal orbit using the low-thrust Reaction Control System (RCS), and targeting a hyperbolic orbit. This paper will describe the design and implementation of the TF algorithm, the strategy to handle EO in various flight regimes, algorithms to cover off-nominal conditions, and other enhancements to the Block-1 PEG algorithm. This paper illustrates challenges posed by the Block-1B vehicle, and results show that the improved PEG algorithm is capable for use on the SLS Block 1-B vehicle as part of the Guidance, Navigation, and Control System.

Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors

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

Kumar, Shiva; Pioszak, Augen; Zhang, Chenghai

2012-02-21

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology ofmore » the ECD and a distinct mode of ligand recognition. Here we report a 1.9 {angstrom} crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.« less

Mitochondrial haplogroups associated with Japanese centenarians, Alzheimer's patients, Parkinson's patients, type 2 diabetic patients and healthy non-obese young males.

PubMed

Takasaki, Shigeru

2009-07-01

The relationships between five classes of Japanese people (i.e., 96 centenarians, 96 Alzheimer's disease (AD) patients, 96 Parkinson's disease (PD) patients, 96 type 2 diabetic (T2D) patients, and 96 healthy non-obese young males) and their mitochondrial single nucleotide polymorphism (mtSNP) frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function (RBF) network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups: Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4c1, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8a1, G, D4, and F1; and Japanese healthy non-obese young males- D4g and D4b1b. From the points of common haplogroups among the five classes, the centenarians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians (over 105 years old) recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person's mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.

Piezoelectret-based hydrophone: an alternative device for vibro-acoustography

NASA Astrophysics Data System (ADS)

de Medeiros, L. J.; Kamimura, H. A. S.; Altafim, R. A. P.; Carneiro, A. A. O.; Amorim, M. F.; Altafim, R. A. C.

2015-09-01

Piezoelectric polymers are highly desirable for ultrasound applications since their low acoustic impedance is much closer to the impedances of air and water than those of traditional piezoceramics. However, the piezoelectric effect observed in these poled polymers is limited to a few dozen picocoulombs per newton and requires very low-noise amplification. A different class of polymeric material known as piezoelectrets, presents piezoelectric effect in the same order of magnitude as those found on piezoceramics. This new class of materials has been explored in a wide range of applications such as flexible keyboards and airborne ultrasound transducers. Based on these polymers, we present here a new transducer for vibro-acoustography (VA), which is an ultrasonic image technique employed in medical diagnosis or material analysis based on ultrasound scattered by a target object. A calibration was carried out using a standard hydrophone, which is normally employed in VA. The average sensitivity of the transducer in the continuous wave mode was 1.712 mV Pa-1(-182.7 dB re 1 V μ Pa-1) with a maximum sensitivity of 18.25 mV Pa-1 (-154.8 dB re 1 V μ Pa-1) at its resonance frequency around 40 kHz. Subsequently, measurements in the burst mode and of directional sensitivity were taken and are presented here together with VA images obtained from a chicken bone and a metal sphere.

NASA's Space Launch System: An Evolving Capability for Exploration An Evolving Capability for Exploration

NASA Technical Reports Server (NTRS)

Creech, Stephen D.; Crumbly, Christopher M.; Robinson, Kimerly F.

2016-01-01

A foundational capability for international human deep-space exploration, NASA's Space Launch System (SLS) vehicle represents a new spaceflight infrastructure asset, creating opportunities for mission profiles and space systems that cannot currently be executed. While the primary purpose of SLS, which is making rapid progress towards initial launch readiness in two years, will be to support NASA's Journey to Mars, discussions are already well underway regarding other potential utilization of the vehicle's unique capabilities. In its initial Block 1 configuration, capable of launching 70 metric tons (t) to low Earth orbit (LEO), SLS is capable of propelling the Orion crew vehicle to cislunar space, while also delivering small CubeSat-class spacecraft to deep-space destinations. With the addition of a more powerful upper stage, the Block 1B configuration of SLS will be able to deliver 105 t to LEO and enable more ambitious human missions into the proving ground of space. This configuration offers opportunities for launching co-manifested payloads with the Orion crew vehicle, and a class of secondary payloads, larger than today's CubeSats. Further upgrades to the vehicle, including advanced boosters, will evolve its performance to 130 t in its Block 2 configuration. Both Block 1B and Block 2 also offer the capability to carry 8.4- or 10-m payload fairings, larger than any contemporary launch vehicle. With unmatched mass-lift capability, payload volume, and C3, SLS not only enables spacecraft or mission designs currently impossible with contemporary EELVs, it also offers enhancing benefits, such as reduced risk, operational costs and/or complexity, shorter transit time to destination or launching large systems either monolithically or in fewer components. This paper will discuss both the performance and capabilities of Space Launch System as it evolves, and the current state of SLS utilization planning.

Broad advances in understanding HIV resistance to antiretrovirals: report on the XVII International HIV Drug Resistance Workshop.

PubMed

Mascolini, Mark; Larder, Brendan A; Boucher, Charles A B; Richman, Douglas D; Mellors, John W

2008-01-01

The 2008 International HIV Drug Resistance Workshop explored six topics on viral resistance: new antiretrovirals; clinical implications; epidemiology; new technologies and interpretations; HIV pathogenesis, fitness, and resistance; and mechanisms of resistance. The last of these topics provided a forum for new work on resistance of hepatitis B and C viruses, which were also explored in two poster sessions. Much work focused on resistance to the two most recent antiretroviral classes (integrase inhibitors and CCR5 antagonists), a new set of entry inhibitor candidates and one new class represented by the maturation inhibitor bevirimat. Other research explored two novel non-nucleoside reverse transcriptase inhibitors, etravirine and IDX899. Epidemiological work analysed rates of transmitted resistant virus, multiclass resistance in antiretroviral-experienced patients and a heightened resistance risk in injecting drug users regardless of adherence. New research on resistance technologies involved an enhanced assay for HIV-1 coreceptor determination and improved gene-based tools for predicting coreceptor use. In the pathogenesis arena, a small study of intensification shed light on the likely source of residual viraemia in patients on successful antiretroviral therapy. A large study in Mozambique correlated the timing of infant infection with selection, transmission and persistence of nevirapine resistance mutations. Mechanistic research explored resistance to the integrase inhibitor raltegravir, K65R-mediated resistance to tenofovir and the role of connection domain mutations in resistance to zidovudine.

Incidence of antimicrobial-resistance genes and integrons in antibiotic-resistant bacteria isolated from eels and aquaculture ponds.

PubMed

Lin, Mao; Wu, Xiaomei; Yan, Qingpi; Ma, Ying; Huang, Lixing; Qin, Yingxue; Xu, Xiaojin

2016-07-07

The overuse of antimicrobials in aquaculture has promoted the selection of antimicrobial-resistant bacteria. Here we investigated the abundance of antimicrobial-resistance genes and integrons in 108 strains of antibiotic-resistant bacteria isolated from eels and aquaculture ponds in China. Conventional PCR was implemented to examine common antibiotic-resistance genes, integrons, and their gene cassette arrays. The results showed that the antibiotic-resistance genes blaTEM, tetC, sulI, aadA, floR, and qnrB were detected at high percentages, as were a number of other resistance genes. Class I integrons were present in 79.63% of the strains, and 10 out of 108 isolates carried class II integrons. Class III integrons were not detected. Three strains carried both class I and class II integrons, and 73.26% of the class I integron-positive isolates contained the qacEΔ1/sul1 gene. Fourteen types of integron cassette arrays were found among class I integron-positive isolates. A new array, dfrB4-catB3-blaOXA-10-aadA1, was discovered in this study. The gene cassette array dfrA12-orfF-aadA2 was the most widely distributed. In summary, 23 different gene cassettes encoding resistance to 8 classes of antibiotics were identified in the class I integrons, and the main cassettes contained genes encoding resistance to aminoglycosides (aad) and trimethoprim (dfr). All class II integron-positive strains had only a single gene cassette array, viz. dfrA1-catB2-sat2-aadA1. High levels of antimicrobial-resistance genes and integrons in eels and auqauculture ponds suggest that the overuse of antimicrobials should be strictly controlled and that the levels of bacterial antimicrobial-resistance genes in aquaculture should be monitored.

Spatial distribution of 12 class B notifiable infectious diseases in China: A retrospective study.

PubMed

Zhu, Bin; Fu, Yang; Liu, Jinlin; Mao, Ying

2018-01-01

China is the largest developing country with a relatively developed public health system. To further prevent and eliminate the spread of infectious diseases, China has listed 39 notifiable infectious diseases characterized by wide prevalence or great harm, and classified them into classes A, B, and C, with severity decreasing across classes. Class A diseases have been almost eradicated in China, thus making class B diseases a priority in infectious disease prevention and control. In this retrospective study, we analyze the spatial distribution patterns of 12 class B notifiable infectious diseases that remain active all over China. Global and local Moran's I and corresponding graphic tools are adopted to explore and visualize the global and local spatial distribution of the incidence of the selected epidemics, respectively. Inter-correlations of clustering patterns of each pair of diseases and a cumulative summary of the high/low cluster frequency of the provincial units are also provided by means of figures and maps. Of the 12 most commonly notifiable class B infectious diseases, viral hepatitis and tuberculosis show high incidence rates and account for more than half of the reported cases. Almost all the diseases, except pertussis, exhibit positive spatial autocorrelation at the provincial level. All diseases feature varying spatial concentrations. Nevertheless, associations exist between spatial distribution patterns, with some provincial units displaying the same type of cluster features for two or more infectious diseases. Overall, high-low (unit with high incidence surrounded by units with high incidence, the same below) and high-high spatial cluster areas tend to be prevalent in the provincial units located in western and southwest China, whereas low-low and low-high spatial cluster areas abound in provincial units in north and east China. Despite the various distribution patterns of 12 class B notifiable infectious diseases, certain similarities between their spatial distributions are present. Substantial evidence is available to support disease-specific, location-specific, and disease-combined interventions. Regarding provinces that show high-high/high-low patterns of multiple diseases, comprehensive interventions targeting different diseases should be established. As to the adjacent provincial units revealing similar patterns, coordinated actions need to be taken across borders.

The Maize PI/GLO Ortholog Zmm16/sterile tassel silky ear1 Interacts with the Zygomorphy and Sex Determination Pathways in Flower Development[OPEN

PubMed Central

Bartlett, Madelaine E.; Williams, Steven K.; Taylor, Zac; DeBlasio, Stacy; Hall, Darren H.; Schmidt, Robert J.; Jackson, David P.

2015-01-01

In monocots and eudicots, B class function specifies second and third whorl floral organ identity as described in the classic ABCE model. Grass B class APETALA3/DEFICIENS orthologs have been functionally characterized; here, we describe the positional cloning and characterization of a maize (Zea mays) PISTILLATA/GLOBOSA ortholog Zea mays mads16 (Zmm16)/sterile tassel silky ear1 (sts1). We show that, similar to many eudicots, all the maize B class proteins bind DNA as obligate heterodimers and positively regulate their own expression. However, sts1 mutants have novel phenotypes that provide insight into two derived aspects of maize flower development: carpel abortion and floral asymmetry. Specifically, we show that carpel abortion acts downstream of organ identity and requires the growth-promoting factor grassy tillers1 and that the maize B class genes are expressed asymmetrically, likely in response to zygomorphy of grass floral primordia. Further investigation reveals that floral phyllotactic patterning is also zygomorphic, suggesting significant mechanistic differences with the well-characterized models of floral polarity. These unexpected results show that despite extensive study of B class gene functions in diverse flowering plants, novel insights can be gained from careful investigation of homeotic mutants outside the core eudicot model species. PMID:26518212

A 3-tier classification of cerebral arteriovenous malformations. Clinical article.

PubMed

Spetzler, Robert F; Ponce, Francisco A

2011-03-01

The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored. Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades. Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively). Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.

Molecular characterization of class b carbapenemases in advanced stage of dissemination and emergence of class d carbapenemases in Enterobacteriaceae from Croatia.

PubMed

Bedenić, Branka; Sardelić, Sanda; Luxner, Josefa; Bošnjak, Zrinka; Varda-Brkić, Dijana; Lukić-Grlić, Amarela; Mareković, Ivana; Frančula-Zaninović, Sonja; Krilanović, Marija; Šijak, Dorotea; Grisold, Andrea; Zarfel, Gernot

2016-09-01

Carbapenemases involved in acquired carbapenem resistance in Enterobacteriaceae belong to Ambler class A serin β-lactamases, class B metallo-β-lactamases (MBL) or class D OXA-48-like β-lactamases. The aim of the present study was to analyse the molecular epidemiology and the mechanisms and routes of spread of class B and class D carbapenemases in Croatia. In total 68 isolates were analyzed. Antibiotic susceptibility was determined by broth microdilution method. PCR was used to detect antibiotic-resistance genes. Genotyping was performed by rep-PCR and MLST. Sixty-five isolates were found to harbour VIM-1 carbapenemase, seven of which were positive also for NDM-1, while two strains harboured only NDM-1. OXA-48 was detected in three isolates, two of which coproduced VIM-1. Thirty-six strains possessed additional CTX-M-15 β-lactamase whereas 64 were positive for TEM-1. CMY was found in 18 Citrobacter freundii isolates and DHA-1 in one Enterobacter cloacae isolate. Four different plasmid-incompatibility groups were found: A/C, L/M, N and FIIAs. Unlike C. freundii and E. cloacae, Klebsiella pneumoniae showed high diversity of rep-PCR patterns. E. cloacae and C. freundii predominantly belonged to one large clone which was allocated to ST105 and ST24, respectively. Three different types of carbapenemases were identified showing the complexity of CRE in Croatia. Copyright © 2016 Elsevier B.V. All rights reserved.

Human Exploration of Earth's Neighborhood and Mars

NASA Technical Reports Server (NTRS)

Condon, Gerald

2003-01-01

The presentation examines Mars landing scenarios, Earth to Moon transfers comparing direct vs. via libration points. Lunar transfer/orbit diagrams, comparison of opposition class and conjunction class missions, and artificial gravity for human exploration missions. Slides related to Mars landing scenarios include: mission scenario; direct entry landing locations; 2005 opportunity - Type 1; Earth-mars superior conjunction; Lander latitude accessibility; Low thrust - Earth return phase; SEP Earth return sequence; Missions - 200, 2007, 2009; and Mission map. Slides related to Earth to Moon transfers (direct vs. via libration points (L1, L2) include libration point missions, expeditionary vs. evolutionary, Earth-Moon L1 - gateway for lunar surface operations, and Lunar mission libration point vs. lunar orbit rendezvous (LOR). Slides related to lunar transfer/orbit diagrams include: trans-lunar trajectory from ISS parking orbit, trans-Earth trajectories, parking orbit considerations, and landing latitude restrictions. Slides related to comparison of opposition class (short-stay) and conjunction class (long-stay) missions for human exploration of Mars include: Mars mission planning, Earth-Mars orbital characteristics, delta-V variations, and Mars mission duration comparison. Slides related to artificial gravity for human exploration missions include: current configuration, NEP thruster location trades, minor axis rotation, and example load paths.

Fatigue behavior of railcar wheel steel at ambient and elevated temperature

DOT National Transportation Integrated Search

2003-08-01

This report presents the results of a material property test program undertaken on a Class B railcar wheel steel. This work was performed to obtain relevant fatigue data that may be used in support of a larger effort exploring the applicability of fa...

77 FR 59423 - Self-Regulatory Organizations; NYSE MKT LLC; Order Granting Approval of a Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... change the relative economic and voting rights of and among Class B Members, by its terms it cannot impact the aggregate economic and voting rights of Class B Members in relation to Class A Members. On... Securities Exchange Act of 1934 (the ``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to...

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class... 47 Telecommunication 4 2014-10-01 2014-10-01 false Contour protection for short-spaced assignments... protected contours, for the purpose of this section, are defined as follows. For all Class B and B1 stations...

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. – NASA astronaut candidates Jessica Meir, Christina Hammock, Anne McClain and Josh Cassada listen to details about Launch Complex 39B at NASA's Kennedy Space Center during a daylong set of briefings and tours of different facilities at NASA's primary launch center. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

Merging separately established stimulus classes with outcome-specific reinforcement.

PubMed

Johnson, Cammarie; Meleshkevich, Olga; Dube, William V

2014-01-01

This study extended previous research on equivalence relations established with outcome-specific reinforcers to include the merger of separately established stimulus classes. Participants were four adults. Conditional discriminations AC and BC were trained first. Correct selections of C1 (C2, or C3) in the presence of A1 or B1 (A2 or B2, or A3 or B3) were followed by red (blue, or white) tokens; tokens were exchanged for value added to three participant-selected gift cards. Outcomes on equivalence tests for three-member classes ABC were positive. DF and EF were trained with the same reinforcing consequences, and tests were positive for three-member classes DEF. Results of class merger tests with combinations of stimuli from the ABC and DEF classes (AD, FB, etc.) were immediately positive for two participants, demonstrating six-member classes ABCDEF with reinforcers as nodes. Merger tests for a third participant were initially negative but became positive after brief exposure to unreinforced probe trials with reinforcers as comparison stimuli. Following class merger, tests for matching the reinforcers to samples and comparisons were also positive. Class-merger test results were negative for a fourth participant. The results provide the first demonstration of eight-member equivalence classes including two outcome-specific conditioned reinforcing stimuli. © Society for the Experimental Analysis of Behavior.

47 CFR 36.331 - Information origination/termination expenses-Account 6310 (Class B telephone companies); Accounts...

Code of Federal Regulations, 2010 CFR

2010-10-01

... telephone companies). (a) The expenses in this account are classified as follows: (1) Other Information... 47 Telecommunication 2 2010-10-01 2010-10-01 false Information origination/termination expenses-Account 6310 (Class B telephone companies); Accounts 6311, 6341, 6351, and 6362 (Class A telephone...

Novel environmental class 1 integrons and cassette arrays recovered from an on-farm bio-purification plant.

PubMed

Martini, María Carla; Quiroga, María Paula; Pistorio, Mariano; Lagares, Antonio; Centrón, Daniela; Del Papa, María Florencia

2018-03-01

Rapid dissemination and emergence of novel antibiotic resistance genes among bacteria are rising problems worldwide. Since their discovery in clinical isolates in the late 1980s, class 1 integrons have been found in a wide range of bacterial genera and have been extensively studied as contributors to dissemination of antibiotic resistance. The present study aimed to investigate the presence and structure of class 1 integrons in plasmid-carrying bacterial isolates obtained from a biopurification system used for decontamination of pesticide-contaminated water as well as their possible role as reservoir of antimicrobial resistance gene cassettes. A total of 35 representative isolates were screened for the presence of class 1 integron integrase encoded by intI1. PCR and DNA sequencing revealed the presence of six class 1 integrons with four variable regions: 5΄CS-aadA1b-3΄CS, 5΄CS-aadA2-3΄CS, 5΄CS-aadA11cΔ-3΄CS and 5΄CS-dfrB3-aadA1di-catB2-aadA6k-3΄CS, the last two being unseen arrays of antimicrobial resistance gene cassettes associated with novel environmental alleles of intI1. These four class 1 integrons were identified as being present in four different genera, including Ochrobactrum, and Variovorax, where class 1 integrons have not been previously reported. The results provide evidence of the biopurification systems as a tank of class 1 integron carrying strains and novel environmental class 1 integron integrases associated with antimicrobial resistance gene cassette arrays. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Predominant Occupation of the Class I MHC Molecule H-2Kwm7 with a Single Self-peptide Suggests a Mechanism for its Diabetes-protective Effect

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

Brims, D.; Qian, J; Jarchum, I

2010-01-01

Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of insulin-producing pancreatic {beta} cells. In both humans and the non-obese diabetic (NOD) mouse model of T1D, class II MHC alleles are the primary determinant of disease susceptibility. However, class I MHC genes also influence risk. These findings are consistent with the requirement for both CD{sup 4+} and CD{sup 8+} T cells in the pathogenesis of T1D. Although a large body of work has permitted the identification of multiple mechanisms to explain the diabetes-protective effect of particular class II MHC alleles, studies examining the protective influence ofmore » class I alleles are lacking. Here, we explored this question by performing biochemical and structural analyses of the murine class I MHC molecule H-2K{sup wm7}, which exerts a diabetes-protective effect in NOD mice. We have found that H-2K{sup wm7} molecules are predominantly occupied by the single self-peptide VNDIFERI, derived from the ubiquitous protein histone H2B. This unexpected finding suggests that the inability of H-2K{sup wm7} to support T1D development could be due, at least in part, to the failure of peptides from critical {beta}-cell antigens to adequately compete for binding and be presented to T cells. Predominant presentation of a single peptide would also be expected to influence T-cell selection, potentially leading to a reduced ability to select a diabetogenic CD{sup 8+} T-cell repertoire. The report that one of the predominant peptides bound by T1D-protective HLA-A*31 is histone derived suggests the potential translation of our findings to human diabetes-protective class I MHC molecules.« less

32 CFR 1630.16 - Class 1-O: Conscientious objector to all military service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Class 1-O: Conscientious objector to all... SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.16 Class 1-O: Conscientious objector to all military... and service in the Armed Forces shall be classified in Class 1-O. (b) Upon the written request of the...

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Sloan, M A; Alexandrov, A V; Tegeler, C H; Spencer, M P; Caplan, L R; Feldmann, E; Wechsler, L R; Newell, D W; Gomez, C R; Babikian, V L; Lefkowitz, D; Goldman, R S; Armon, C; Hsu, C Y; Goodin, D S

2004-05-11

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Ship noise extends to frequencies used for echolocation by endangered killer whales.

PubMed

Veirs, Scott; Veirs, Val; Wood, Jason D

2016-01-01

Combining calibrated hydrophone measurements with vessel location data from the Automatic Identification System, we estimate underwater sound pressure levels for 1,582 unique ships that transited the core critical habitat of the endangered Southern Resident killer whales during 28 months between March, 2011, and October, 2013. Median received spectrum levels of noise from 2,809 isolated transits are elevated relative to median background levels not only at low frequencies (20-30 dB re 1 µPa(2)/Hz from 100 to 1,000 Hz), but also at high frequencies (5-13 dB from 10,000 to 96,000 Hz). Thus, noise received from ships at ranges less than 3 km extends to frequencies used by odontocetes. Broadband received levels (11.5-40,000 Hz) near the shoreline in Haro Strait (WA, USA) for the entire ship population were 110 ± 7 dB re 1 µPa on average. Assuming near-spherical spreading based on a transmission loss experiment we compute mean broadband source levels for the ship population of 173 ± 7 dB re 1 µPa 1 m without accounting for frequency-dependent absorption. Mean ship speed was 7.3 ± 2.0 m/s (14.1 ± 3.9 knots). Most ship classes show a linear relationship between source level and speed with a slope near +2 dB per m/s (+1 dB/knot). Spectrum, 1/12-octave, and 1/3-octave source levels for the whole population have median values that are comparable to previous measurements and models at most frequencies, but for select studies may be relatively low below 200 Hz and high above 20,000 Hz. Median source spectrum levels peak near 50 Hz for all 12 ship classes, have a maximum of 159 dB re 1 µPa(2)/Hz @ 1 m for container ships, and vary between classes. Below 200 Hz, the class-specific median spectrum levels bifurcate with large commercial ships grouping as higher power noise sources. Within all ship classes spectrum levels vary more at low frequencies than at high frequencies, and the degree of variability is almost halved for classes that have smaller speed standard deviations. This is the first study to present source spectra for populations of different ship classes operating in coastal habitats, including at higher frequencies used by killer whales for both communication and echolocation.

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

9 CFR 78.10 - Official vaccination of cattle moving into and out of Class B and Class C States or areas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Official vaccination of cattle moving... Because of Brucellosis § 78.10 Official vaccination of cattle moving into and out of Class B and Class C... slaughtering establishment. Female cattle eligible for official calfhood vaccination and required by this...

9 CFR 78.10 - Official vaccination of cattle moving into and out of Class B and Class C States or areas.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Official vaccination of cattle moving... Because of Brucellosis § 78.10 Official vaccination of cattle moving into and out of Class B and Class C... slaughtering establishment. Female cattle eligible for official calfhood vaccination and required by this...

9 CFR 78.10 - Official vaccination of cattle moving into and out of Class B and Class C States or areas.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Official vaccination of cattle moving... Because of Brucellosis § 78.10 Official vaccination of cattle moving into and out of Class B and Class C... slaughtering establishment. Female cattle eligible for official calfhood vaccination and required by this...

9 CFR 78.10 - Official vaccination of cattle moving into and out of Class B and Class C States or areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Official vaccination of cattle moving... Because of Brucellosis § 78.10 Official vaccination of cattle moving into and out of Class B and Class C... slaughtering establishment. Female cattle eligible for official calfhood vaccination and required by this...

9 CFR 78.10 - Official vaccination of cattle moving into and out of Class B and Class C States or areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Official vaccination of cattle moving... Because of Brucellosis § 78.10 Official vaccination of cattle moving into and out of Class B and Class C... slaughtering establishment. Female cattle eligible for official calfhood vaccination and required by this...

Impacts of tilling and covering treatments on the biosolids solar drying conversion from Class B to Class A

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the effects of tillage and cover treatments of solar drying on the conversion of Class B treated sewage sludge to a Class A product. The experiments were performed over two years at Green Valley, Arizona in steel-constructed sand-filled drying beds of 1.0m...

NASA's Space Launch System: An Evolving Capability for Exploration

NASA Technical Reports Server (NTRS)

Creech, Stephen D.; Robinson, Kimberly F.

2016-01-01

A foundational capability for international human deep-space exploration, NASA's Space Launch System (SLS) vehicle represents a new spaceflight infrastructure asset, creating opportunities for mission profiles and space systems that cannot currently be executed. While the primary purpose of SLS, which is making rapid progress towards initial launch readiness in two years, will be to support NASA's Journey to Mars, discussions are already well underway regarding other potential utilization of the vehicle's unique capabilities. In its initial Block 1 configuration, capable of launching 70 metric tons (t) to low Earth orbit (LEO), SLS will propel the Orion crew vehicle to cislunar space, while also delivering small CubeSat-class spacecraft to deep-space destinations. With the addition of a more powerful upper stage, the Block 1B configuration of SLS will be able to deliver 105 t to LEO and enable more ambitious human missions into the proving ground of space. This configuration offers opportunities for launching co-manifested payloads with the Orion crew vehicle, and a class of secondary payloads, larger than today's CubeSats. Further upgrades to the vehicle, including advanced boosters, will evolve its performance to 130 t in its Block 2 configuration. Both Block 1B and Block 2 also offer the capability to carry 8.4- or 10-m payload fairings, larger than any contemporary launch vehicle. With unmatched mass-lift capability, payload volume, and C3, SLS not only enables spacecraft or mission designs currently impossible with contemporary EELVs, it also offers enhancing benefits, such as reduced risk, operational costs and/or complexity, shorter transit time to destination or launching large systems either monolithically or in fewer components. This paper will discuss both the performance and capabilities of Space Launch System as it evolves, and the current state of SLS utilization planning.

Molecular Recognition of Corticotropin releasing Factor by Its G protein-coupled Receptor CRFR1

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

Pioszak, Augen A.; Parker, Naomi R.; Suino-Powell, Kelly

2009-01-15

The bimolecular interaction between corticotropin-releasing factor (CRF), a neuropeptide, and its type 1 receptor (CRFR1), a class B G-protein-coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form and two in distinct CRF-bound states. The CRFR1 ECD adopts the alpha-beta-betaalpha fold observedmore » for other class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide-binding site of other class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.« less

48 CFR 1.703 - Class determinations and findings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... findings. 1.703 Section 1.703 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Determinations and Findings 1.703 Class determinations and findings... identical justification. (b) The findings in a class D&F shall fully support the proposed action either for...

Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities.

PubMed

Doe, Chris; Bentley, Ross; Behm, David J; Lafferty, Robert; Stavenger, Robert; Jung, David; Bamford, Mark; Panchal, Terry; Grygielko, Eugene; Wright, Lois L; Smith, Gary K; Chen, Zunxuan; Webb, Christine; Khandekar, Sanjay; Yi, Tracey; Kirkpatrick, Robert; Dul, Edward; Jolivette, Larry; Marino, Joseph P; Willette, Robert; Lee, Dennis; Hu, Erding

2007-01-01

Increased Rho kinase (ROCK) activity contributes to smooth muscle contraction and regulates blood pressure homeostasis. We hypothesized that potent and selective ROCK inhibitors with novel structural motifs would help elucidate the functional role of ROCK and further explore the therapeutic potential of ROCK inhibition for hypertension. In this article, we characterized two aminofurazan-based inhibitors, GSK269962A [N-(3-{[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo[4, 5-c]pyridin-6-yl]oxy}phenyl)-4-{[2-(4-morpholinyl)ethyl]-oxy}benzamide] and SB-7720770-B [4-(7-{[(3S)-3-amino-1-pyrrolidinyl]carbonyl}-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine], as members of a novel class of compounds that potently inhibit ROCK enzymatic activity. GSK269962A and SB-772077-B have IC50 values of 1.6 and 5.6 nM toward recombinant human ROCK1, respectively. GSK269962A also exhibited more than 30-fold selectivity against a panel of serine/threonine kinases. In lipopolysaccharide-stimulated monocytes, these inhibitors blocked the generation of inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha. Furthermore, both SB-772077-B and GSK269962A induced vasorelaxation in preconstricted rat aorta with an IC50 of 39 and 35 nM, respectively. Oral administration of either GSK269962A or SB-772077-B produced a profound dose-dependent reduction of systemic blood pressure in spontaneously hypertensive rats. At doses of 1, 3, and 30 mg/kg, both compounds induced a reduction in blood pressure of approximately 10, 20, and 50 mm Hg. In addition, administration of SB-772077-B also dramatically lowered blood pressure in DOCA salt-induced hypertensive rats. SB-772077-B and GSK269962A represent a novel class of ROCK inhibitors that have profound effects in the vasculature and may enable us to further evaluate the potential beneficial effects of ROCK inhibition in animal models of cardiovascular as well as other chronic diseases.

Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides.

PubMed

Kessler, Jan H; Mommaas, Bregje; Mutis, Tuna; Huijbers, Ivo; Vissers, Debby; Benckhuijsen, Willemien E; Schreuder, Geziena M Th; Offringa, Rienk; Goulmy, Els; Melief, Cornelis J M; van der Burg, Sjoerd H; Drijfhout, Jan W

2003-02-01

We report the development, validation, and application of competition-based peptide binding assays for 13 prevalent human leukocyte antigen (HLA) class I alleles. The assays are based on peptide binding to HLA molecules on living cells carrying the particular allele. Competition for binding between the test peptide of interest and a fluorescein-labeled HLA class I binding peptide is used as read out. The use of cell membrane-bound HLA class I molecules circumvents the need for laborious biochemical purification of these molecules in soluble form. Previously, we have applied this principle for HLA-A2 and HLA-A3. We now describe the assays for HLA-A1, HLA-A11, HLA-A24, HLA-A68, HLA-B7, HLA-B8, HLA-B14, HLA-B35, HLA-B60, HLA-B61, and HLA-B62. Together with HLA-A2 and HLA-A3, these alleles cover more than 95% of the Caucasian population. Several allele-specific parameters were determined for each assay. Using these assays, we identified novel HLA class I high-affinity binding peptides from HIVpol, p53, PRAME, and minor histocompatibility antigen HA-1. Thus these convenient and accurate peptide-binding assays will be useful for the identification of putative cytotoxic T lymphocyte epitopes presented on a diverse array of HLA class I molecules.

The Maize PI/GLO Ortholog Zmm16/sterile tassel silky ear1 Interacts with the Zygomorphy and Sex Determination Pathways in Flower Development.

PubMed

Bartlett, Madelaine E; Williams, Steven K; Taylor, Zac; DeBlasio, Stacy; Goldshmidt, Alexander; Hall, Darren H; Schmidt, Robert J; Jackson, David P; Whipple, Clinton J

2015-11-01

In monocots and eudicots, B class function specifies second and third whorl floral organ identity as described in the classic ABCE model. Grass B class APETALA3/DEFICIENS orthologs have been functionally characterized; here, we describe the positional cloning and characterization of a maize (Zea mays) PISTILLATA/GLOBOSA ortholog Zea mays mads16 (Zmm16)/sterile tassel silky ear1 (sts1). We show that, similar to many eudicots, all the maize B class proteins bind DNA as obligate heterodimers and positively regulate their own expression. However, sts1 mutants have novel phenotypes that provide insight into two derived aspects of maize flower development: carpel abortion and floral asymmetry. Specifically, we show that carpel abortion acts downstream of organ identity and requires the growth-promoting factor grassy tillers1 and that the maize B class genes are expressed asymmetrically, likely in response to zygomorphy of grass floral primordia. Further investigation reveals that floral phyllotactic patterning is also zygomorphic, suggesting significant mechanistic differences with the well-characterized models of floral polarity. These unexpected results show that despite extensive study of B class gene functions in diverse flowering plants, novel insights can be gained from careful investigation of homeotic mutants outside the core eudicot model species. © 2015 American Society of Plant Biologists. All rights reserved.

Ligand Recognition by A-Class Eph Receptors: Crystal Structures of the EphA2 Ligand-Binding Domain and the EphA2/ephrin-A1 Complex

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

Himanen, J.; Goldgur, Y; Miao, H

2009-01-01

Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B) according to preferences for their ephrin ligands. All published structural studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we present the crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2. Although these structures are similar overall to their B-class counterparts, they reveal important differences that define subclass specificity. The structures suggest that the A-class Eph receptor/ephrin interactions involve smaller rearrangements in the interacting partners, better described by a 'lock-and-key'-type binding mechanism, in contrast to the 'induced fit' mechanism defining the B-class molecules.more » This model is supported by structure-based mutagenesis and by differential requirements for ligand oligomerization by the two subclasses in cell-based Eph receptor activation assays. Finally, the structure of the unligated receptor reveals a homodimer assembly that might represent EphA2-specific homotypic cell adhesion interactions.« less

Electrodynamics and radiofrequency antenna concepts for human magnetic resonance at 23.5 T (1 GHz) and beyond.

PubMed

Winter, Lukas; Niendorf, Thoralf

2016-06-01

This work investigates electrodynamic constraints, explores RF antenna concepts and examines the transmission fields (B 1 (+) ) and RF power deposition of dipole antenna arrays for (1)H magnetic resonance of the human brain at 1 GHz (23.5 T). Electromagnetic field (EMF) simulations are performed in phantoms with average tissue simulants for dipole antennae using discrete frequencies [300 MHz (7.0 T) to 3 GHz (70.0 T)]. To advance to a human setup EMF simulations are conducted in anatomical human voxel models of the human head using a 20-element dipole array operating at 1 GHz. Our results demonstrate that transmission fields suitable for (1)H MR of the human brain can be achieved at 1 GHz. An increase in transmit channel density around the human head helps to enhance B 1 (+) in the center of the brain. The calculated relative increase in specific absorption rate at 23.5 versus 7.0 T was below 1.4 (in-phase phase setting) and 2.7 (circular polarized phase setting) for the dipole antennae array. The benefits of multi-channel dipole antennae at higher frequencies render MR at 23.5 T feasible from an electrodynamic standpoint. This very preliminary finding opens the door on further explorations that might be catalyzed into a 20-T class human MR system.

Refolding of β-Stranded Class I Chitinases of Hippophae rhamnoides Enhances the Antifreeze Activity during Cold Acclimation

PubMed Central

Gupta, Ravi; Deswal, Renu

2014-01-01

Class I chitinases hydrolyse the β-1,4-linkage of chitin and also acquire antifreeze activity in some of the overwintering plants during cold stress. Two chitinases, HrCHT1a of 31 kDa and HrCHT1b of 34 kDa, were purified from cold acclimated and non-acclimated seabuckthorn seedlings using chitin affinity chromatography. 2-D gels of HrCHT1a and HrCHT1b showed single spots with pIs 7.0 and 4.6 respectively. N-terminal sequence of HrCHT1b matched with the class I chitinase of rice and antifreeze proteins while HrCHT1a could not be sequenced as it was N-terminally blocked. Unlike previous reports, where antifreeze activity of chitinase was cold inducible, our results showed that antifreeze activity is constitutive property of class I chitinase as both HrCHT1a and HrCHT1b isolated even from non-acclimated seedlings, exhibited antifreeze activity. Interestingly, HrCHT1a and HrCHT1b purified from cold acclimated seedlings, exhibited 4 and 2 times higher antifreeze activities than those purified from non-acclimated seedlings, suggesting that antifreeze activity increased during cold acclimation. HrCHT1b exhibited 23–33% higher hydrolytic activity and 2–4 times lower antifreeze activity than HrCHT1a did. HrCHT1b was found to be a glycoprotein; however, its antifreeze activity was independent of glycosylation as even deglycosylated HrCHT1b exhibited antifreeze activity. Circular dichroism (CD) analysis showed that both these chitinases were rich in unusual β-stranded conformation (36–43%) and the content of β-strand increased (∼11%) during cold acclimation. Surprisingly, calcium decreased both the activities of HrCHT1b while in case of HrCHT1a, a decrease in the hydrolytic activity and enhancement in its antifreeze activity was observed. CD results showed that addition of calcium also increased the β-stranded conformation of HrCHT1a and HrCHT1b. This is the first report, which shows that antifreeze activity is constitutive property of class I chitinase and cold acclimation and calcium regulate these activities of chitinases by changing the secondary structure. PMID:24626216

Refolding of β-stranded class I chitinases of Hippophae rhamnoides enhances the antifreeze activity during cold acclimation.

PubMed

Gupta, Ravi; Deswal, Renu

2014-01-01

Class I chitinases hydrolyse the β-1,4-linkage of chitin and also acquire antifreeze activity in some of the overwintering plants during cold stress. Two chitinases, HrCHT1a of 31 kDa and HrCHT1b of 34 kDa, were purified from cold acclimated and non-acclimated seabuckthorn seedlings using chitin affinity chromatography. 2-D gels of HrCHT1a and HrCHT1b showed single spots with pIs 7.0 and 4.6 respectively. N-terminal sequence of HrCHT1b matched with the class I chitinase of rice and antifreeze proteins while HrCHT1a could not be sequenced as it was N-terminally blocked. Unlike previous reports, where antifreeze activity of chitinase was cold inducible, our results showed that antifreeze activity is constitutive property of class I chitinase as both HrCHT1a and HrCHT1b isolated even from non-acclimated seedlings, exhibited antifreeze activity. Interestingly, HrCHT1a and HrCHT1b purified from cold acclimated seedlings, exhibited 4 and 2 times higher antifreeze activities than those purified from non-acclimated seedlings, suggesting that antifreeze activity increased during cold acclimation. HrCHT1b exhibited 23-33% higher hydrolytic activity and 2-4 times lower antifreeze activity than HrCHT1a did. HrCHT1b was found to be a glycoprotein; however, its antifreeze activity was independent of glycosylation as even deglycosylated HrCHT1b exhibited antifreeze activity. Circular dichroism (CD) analysis showed that both these chitinases were rich in unusual β-stranded conformation (36-43%) and the content of β-strand increased (∼11%) during cold acclimation. Surprisingly, calcium decreased both the activities of HrCHT1b while in case of HrCHT1a, a decrease in the hydrolytic activity and enhancement in its antifreeze activity was observed. CD results showed that addition of calcium also increased the β-stranded conformation of HrCHT1a and HrCHT1b. This is the first report, which shows that antifreeze activity is constitutive property of class I chitinase and cold acclimation and calcium regulate these activities of chitinases by changing the secondary structure.

Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors.

PubMed

Mathew, Bijo; Haridas, Abitha; Uçar, Gülberk; Baysal, Ipek; Adeniyi, Adebayo A; Soliman, Mahmoud E S; Joy, Monu; Mathew, Githa Elizabeth; Lakshmanan, Baskar; Jayaprakash, Venkatesan

2016-10-01

Chalcone has been reported to be a valid scaffold for the design of monoamine oxidase (MAO) inhibitors. This scenario has amplified the momentum for the discovery of heteroaryl based chalcone MAO inhibitors. In the present study, we have synthesized a series of eleven chlorinated thienyl chalcone derivatives substituted with a different functional groups at the para- position on the ring B and investigated for their ability to inhibit human MAO-A and -B. With the exception of compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one (TC7), which was a selective MAO-A inhibitor, all the other derivatives inhibited hMAO-B potently and selectively with competitive mode of inhibition. The most potent compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-ethylphenyl)prop-2-en-1-one (TC6) was found to be the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.31±0.02μM and 16.84, respectively. All the compounds presented in the current study are completely non-toxic with 74-88% viable cells to hepatic cells at 100μM concentration. Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.2 and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO-B inhibitor TC6. Copyright © 2016 Elsevier B.V. All rights reserved.

Significant interactions between maternal PAH exposure and single nucleotide polymorphisms in candidate genes on B[ a ]P-DNA adducts in a cohort of non-smoking Polish mothers and newborns.

PubMed

Iyer, Shoba; Wang, Ya; Xiong, Wei; Tang, Deliang; Jedrychowski, Wieslaw; Chanock, Stephen; Wang, Shuang; Stigter, Laura; Mróz, Elzbieta; Perera, Frederica

2016-11-01

Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[ a ]pyrene (B[ a ]P) is a well-studied PAH that is classified as a known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[ a ]P metabolism genes on B[ a ]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking women ( n = 368) with available data on maternal PAH exposure, paired cord adducts, and genetic data who resided in Krakow, Poland. We selected eight common variants in maternal and newborn candidate genes related to B[ a ]P metabolism, detoxification, and repair for our analyses: CYP1A1 , CYP1A2 , CYP1B1 , GSTM1 , GSTT2 , NQO1 , and XRCC1 . We observed significant interactions between maternal PAH exposure and SNPs on cord B[ a ]P-DNA adducts in the following genes: maternal CYP1A1 and GSTT2 , and newborn CYP1A1 and CYP1B1 . These novel findings highlight differences in maternal and newborn genetic contributions to B[ a ]P-DNA adduct formation and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[ a ]P. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules

PubMed Central

Hilton, Hugo G; Parham, Peter

2013-01-01

Monoclonal antibodies with specificity for HLA class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing 3-6 HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with one of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1μg/ml) PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50μg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23, and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets. PMID:23510417

Challenges at Petascale for Pseudo-Spectral Methods on Spheres (A Last Hurrah?)

NASA Technical Reports Server (NTRS)

Clune, Thomas

2011-01-01

Conclusions: a) Proper software abstractions should enable rapid-exploration of platform-specific optimizations/ tradeoffs. b) Pseudo-spectra! methods are marginally viable for at least some classes of petascaie problems. i.e., GPU based machine with good bisection would be best. c) Scalability at exascale is possible, but the necessary resolution will make algorithm prohibitively expensive. Efficient implementations of realistic global transposes are mtricate and tedious in MPI. PS at petascaie requires exploration of a variety of strategies for spreading local and remote communic3tions. PGAS allows far simpler implementation and thus rapid exploration of variants.

On Space Exploration and Human Error: A Paper on Reliability and Safety

NASA Technical Reports Server (NTRS)

Bell, David G.; Maluf, David A.; Gawdiak, Yuri

2005-01-01

NASA space exploration should largely address a problem class in reliability and risk management stemming primarily from human error, system risk and multi-objective trade-off analysis, by conducting research into system complexity, risk characterization and modeling, and system reasoning. In general, in every mission we can distinguish risk in three possible ways: a) known-known, b) known-unknown, and c) unknown-unknown. It is probably almost certain that space exploration will partially experience similar known or unknown risks embedded in the Apollo missions, Shuttle or Station unless something alters how NASA will perceive and manage safety and reliability

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. – NASA astronaut candidates Nicole Mann, Victor Glover, Tyler "Nick" Hague, Andrew Morgan, Christina Hammock, Jessica Meir, Josh Cassada and Anne McClain listen to details about Launch Complex 39B at NASA's Kennedy Space Center during a daylong set of briefings and tours of different facilities at NASA's primary launch center. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

The Role of HLA Class I Gene Variation in Autoimmune Diabetes

PubMed Central

Sia, Charles; Weinem, Michael

2005-01-01

The use of DNA-based genetic typing has enabled the identification of type 1 diabetes mellitus (T1DM) susceptible and protective major histocompatibility complex (MHC) class II alleles and haplotypes. The application of this approach has also progressed to locate MHC class I alleles that contribute to the clinicopathology of T1DM. Recent studies have shown a widespread involvement of genes from the MHC class I gene region in the clinicopathology of T1DM. These genes are shown to be involved in contributing to progression from the preclinical stage of the disease, which is characterized by the occurrence of islet-specific antibodies, to clinical disease and also to the occurrence of autoimmunity. They can either contribute directly to disease development or indirectly in concert with other susceptible MHC class II alleles or haplotypes via linkage disequilibrium. Class I alleles may also be negatively associated with T1DM. These findings are useful for the development of future strategies in designing tolerogenic approaches for the prevention or even reversal of T1DM. In this article, the latest evidence for the different kinds of participation of HLA class I genes in the etiology of T1DM is reviewed. A meta-analysis which included existing association studies was also carried out in order to re-assess the relevance of class I genes in diabetes development. The analysis of an enlarged heterogeneous sample confirmed the involvement of previously detected serotypes in the etiology of T1DM, such as A24, B8 and B18, and revealed hitherto unknown associations with B60 and B62. The analysis points out that much of the conflicting results of previous association studies originate from inadequate sample sizes and accentuate the value of future investigations of larger samples for identifying linkage in multigenic diseases. PMID:17491685

Effects of select and reject control on equivalence class formation and transfer of function.

PubMed

Perez, William F; Tomanari, Gerson Y; Vaidya, Manish

2015-09-01

The present study used a single-subject design to evaluate the effects of select or reject control on equivalence class formation and transfer of function. Adults were exposed to a matching-to-sample task with observing requirements (MTS-OR) in order to bias the establishment of sample/S+ (select) or sample/S- (reject) relations. In Experiment 1, four sets of baseline conditional relations were taught-two under reject control (A1B2C1, A2B1C2) and two under select control (D1E1F1, D2E2F2). Participants were tested for transitivity, symmetry, equivalence and reflexivity. They also learned a simple discrimination involving one of the stimuli from the equivalence classes and were tested for the transfer of the discriminative function. In general, participants performed with high accuracy on all equivalence-related probes as well as the transfer of function probes under select control. Under reject control, participants had high scores only on the symmetry test; transfer of function was attributed to stimuli programmed as S-. In Experiment 2, the equivalence class under reject control was expanded to four members (A1B2C1D2; A2B1C2D1). Participants had high scores only on symmetry and on transitivity and equivalence tests involving two nodes. Transfer of function was extended to the programmed S- added to each class. Results from both experiments suggest that select and reject controls might differently affect the formation of equivalence classes and the transfer of stimulus functions. © Society for the Experimental Analysis of Behavior.

Replacement Non-Toxic Sealants for Standard Chromated Sealants

DTIC Science & Technology

2005-02-01

material’s mechanical or physical properties and resistance to degradation. As sealant formulations for the Class B-2 worklife were developed by PRC...results ofthis testing, Class B-1I2 and C-12 worklife materials were formulated and are being tested. In addition to the testing that UDRI conducted, two...successfully accomplished in this program. An optimized Class B-2 worklife of the sealant compound designated RW3758-71, Lot no. RT0946, completed

Quantitative evaluation of liver cirrhosis using T1 relaxation time with 3 tesla MRI before and after oxygen inhalation.

PubMed

Kim, Kyung Ah; Park, Mi-Suk; Kim, In-Seong; Kiefer, Berthold; Chung, Woo-Suk; Kim, Myeong-Jin; Kim, Ki Whang

2012-08-01

To quantify liver T1 relaxation times before and after oxygen inhalation in patients with and without liver cirrhosis using a 3 Tesla (T) MRI. Institutional Review Board approval and written informed consent were obtained. Ninety-two noncirrhotic patients and 87 patients with hepatitis B viral liver cirrhosis (72 Child-Pugh class A and 15 Child-Pugh class B or C) underwent MRI with a 3.0T system before and after the supply of 100% oxygen at a rate of 15 L/min by means of a nonrebreather ventilation mask for 3 min. T1 maps were acquired using three-dimensional spoiled gradient echo sequences with two different flip angles (2° and 14°) and a fixed TR/TE (2.54 ms/0.95 ms). Liver T1 values were obtained using a T1 processing tool (MapIT software). The mean baseline T1 values of three groups (control, Child-Pugh class A, and Child-Pugh class B/C) were compared using an analysis of variance test. Liver T1 value before and after oxygenation was compared using a paired t-test for each group. The baseline liver T1 value was significantly higher in the control group (941 ± 136 ms) than in Child-Pugh A (858 ± 143 ms) and Child-Pugh B/C (783 ± 164 ms) group (P < 0.001 and P < 0.0001). The reduction in the liver T1 value after oxygen inhalation was significant in the control group (P = 0.012) but not significant in Child-Pugh class A (P = 0.079) and Child-Pugh class B/C (P = 0.752). The baseline liver T1 relaxation time was significantly different between the patients with and without liver cirrhosis. The shortening effect of oxygen on the liver T1 value was significant in the control group but not in the cirrhotic patients. Copyright © 2012 Wiley Periodicals, Inc.

Explorations; Part I, Revised: Career Activities for Adult Education Classes.

ERIC Educational Resources Information Center

Feingold, S. Norman

The Adult Career Education Resources Survey was designed to (a) compile career information resources for adults and (b) provide materials that will encourage adult educators to integrate career education activities into ongoing curricula. The document was developed and revised by the Suvey staff to meet the second objective; it provides a group of…

A Qualitative Investigation of Student Outcomes in a Residential Learning Community

ERIC Educational Resources Information Center

Blackhurst, Anne E.; Akey, Lynn D.; Bobilya, Andrew J.

2003-01-01

Researchers conducted a qualitative study of students' in- and out-of-class experiences in a residential learning community at a mid-sized public institution. Focus group interviews were conducted to explore (a) the outcomes of learning community membership from participants' point of view and (b) the connections between participants' reported…

Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample

PubMed Central

Hildebrandt, Tom; Epstein, Elizabeth E.; Sysko, Robyn; Bux, Donald A.

2017-01-01

Background The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use. Method We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD. Results Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes. Conclusions The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs. PMID:28247423

Spatial distribution of 12 class B notifiable infectious diseases in China: A retrospective study

PubMed Central

Zhu, Bin; Fu, Yang; Liu, Jinlin

2018-01-01

Background China is the largest developing country with a relatively developed public health system. To further prevent and eliminate the spread of infectious diseases, China has listed 39 notifiable infectious diseases characterized by wide prevalence or great harm, and classified them into classes A, B, and C, with severity decreasing across classes. Class A diseases have been almost eradicated in China, thus making class B diseases a priority in infectious disease prevention and control. In this retrospective study, we analyze the spatial distribution patterns of 12 class B notifiable infectious diseases that remain active all over China. Methods Global and local Moran’s I and corresponding graphic tools are adopted to explore and visualize the global and local spatial distribution of the incidence of the selected epidemics, respectively. Inter-correlations of clustering patterns of each pair of diseases and a cumulative summary of the high/low cluster frequency of the provincial units are also provided by means of figures and maps. Results Of the 12 most commonly notifiable class B infectious diseases, viral hepatitis and tuberculosis show high incidence rates and account for more than half of the reported cases. Almost all the diseases, except pertussis, exhibit positive spatial autocorrelation at the provincial level. All diseases feature varying spatial concentrations. Nevertheless, associations exist between spatial distribution patterns, with some provincial units displaying the same type of cluster features for two or more infectious diseases. Overall, high–low (unit with high incidence surrounded by units with high incidence, the same below) and high–high spatial cluster areas tend to be prevalent in the provincial units located in western and southwest China, whereas low–low and low–high spatial cluster areas abound in provincial units in north and east China. Conclusion Despite the various distribution patterns of 12 class B notifiable infectious diseases, certain similarities between their spatial distributions are present. Substantial evidence is available to support disease-specific, location-specific, and disease-combined interventions. Regarding provinces that show high–high/high–low patterns of multiple diseases, comprehensive interventions targeting different diseases should be established. As to the adjacent provincial units revealing similar patterns, coordinated actions need to be taken across borders. PMID:29621351

Electric Propulsion Options for a Magnetospheric Mapping Mission

NASA Technical Reports Server (NTRS)

Oleson, Steven; Russell, Chris; Hack, Kurt; Riehl, John

1998-01-01

The Twin Electric Magnetospheric Probes Exploring on Spiral Trajectories mission concept was proposed as a Middle Explorer class mission. A pre-phase-A design was developed which utilizes the advantages of electric propulsion for Earth scientific spacecraft use. This paper presents propulsion system analyses performed for the proposal. The proposed mission required two spacecraft to explore near circular orbits 0.1 to 15 Earth radii in both high and low inclination orbits. Since the use of chemical propulsion would require launch vehicles outside the Middle Explorer class a reduction in launch mass was sought using ion, Hall, and arcjet electric propulsion system. Xenon ion technology proved to be the best propulsion option for the mission requirements requiring only two Pegasus XL launchers. The Hall thruster provided an alternative solution but required two larger, Taurus launch vehicles. Arcjet thrusters did not allow for significant launch vehicle reduction in the Middle Explorer class.

HLA class I molecules consistently present internal influenza epitopes.

PubMed

Wahl, Angela; Schafer, Fredda; Bardet, Wilfried; Buchli, Rico; Air, Gillian M; Hildebrand, William H

2009-01-13

Cytotoxic T lymphocytes (CTL) limit influenza virus replication and prevent morbidity and mortality upon recognition of HLA class I presented epitopes on the surface of virus infected cells, yet the number and origin of the viral epitopes that decorate the infected cell are unknown. To understand the presentation of influenza virus ligands by human MHC class I molecules, HLA-B*0702-presented viral peptides were directly identified following influenza infection. After transfection with soluble class I molecules, peptide ligands unique to infected cells were eluted from isolated MHC molecules and identified by comparative mass spectrometry (MS). Then CTL were gathered following infection with influenza and viral peptides were tested for immune recognition. We found that the class I molecule B*0702 presents 3-6 viral ligands following infection with different strains of influenza. Peptide ligands derived from the internal viral nucleoprotein (NP(418-426) and NP(473-481)) and from the internal viral polymerase subunit PB1 (PB1(329-337)) were presented by B*0702 following infection with each of 3 different influenza strains; ligands NP(418-426), NP(473-481), and PB1(329-337) derived from internal viral proteins were consistently revealed by class I HLA. In contrast, ligands derived from hemagglutinin (HA) and matrix protein (M1) were presented intermittently on a strain-by-strain basis. When tested for immune recognition, HLA-B*0702 transgenic mice responded to NP(418-426) and PB1(329-337) consistently and NP(473-481) intermittently while ligands from HA and M1 were not recognized. These data demonstrate an emerging pattern whereby class I HLA reveal a handful of internal viral ligands and whereby CTL recognize consistently presented influenza ligands.

Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP‐1‐derived macrophages

PubMed Central

Wang, Limei; Palme, Veronika; Rotter, Susanne; Schilcher, Nicole; Cukaj, Malsor; Wang, Dongdong; Ladurner, Angela; Heiss, Elke H.; Stangl, Herbert; Dirsch, Verena M.

2016-01-01

1 Scope Increased macrophage cholesterol efflux (ChE) is considered to have anti‐atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP‐1‐derived macrophages, and mechanisms underlying this effect are explored. 2 Methods and results Without affecting cell viability, piperine concentration‐dependently enhances ChE in THP‐1‐derived macrophages from 25 to 100 μM. The expression level of the key cholesterol transporter protein ATP‐binding cassette transporter A1 (ABCA1) is significantly upregulated by piperine, as revealed by western blot analyses. However, two other ChE‐mediating transporter proteins, ATP‐binding cassette transporter G1 (ABCG1) and scavenger receptor class B member 1 (SR‐B1), remain unaffected. Piperine exerts no influence on ABCA1 mRNA levels, but significantly inhibits the degradation of ABCA1, as evident by an increased half‐life of the protein in the presence of cycloheximide. Furthermore, it is found that piperine likely interferes with the calpain‐mediated ABCA1 degradation pathway and exhibits significant inhibition of calpain activity. 3 Conclusion Our findings suggest that piperine promotes ChE in THP‐1‐derived macrophages by upregulation of ABCA1, which might be mediated by inhibition of calpain activity. This novel bioactivity makes the dietary constituent piperine a good candidate to be further explored for therapeutic or preventive applications in the context of atherosclerosis. PMID:27862930

Ship noise extends to frequencies used for echolocation by endangered killer whales

PubMed Central

Veirs, Val; Wood, Jason D.

2016-01-01

Combining calibrated hydrophone measurements with vessel location data from the Automatic Identification System, we estimate underwater sound pressure levels for 1,582 unique ships that transited the core critical habitat of the endangered Southern Resident killer whales during 28 months between March, 2011, and October, 2013. Median received spectrum levels of noise from 2,809 isolated transits are elevated relative to median background levels not only at low frequencies (20–30 dB re 1 µPa2/Hz from 100 to 1,000 Hz), but also at high frequencies (5–13 dB from 10,000 to 96,000 Hz). Thus, noise received from ships at ranges less than 3 km extends to frequencies used by odontocetes. Broadband received levels (11.5–40,000 Hz) near the shoreline in Haro Strait (WA, USA) for the entire ship population were 110 ± 7 dB re 1 µPa on average. Assuming near-spherical spreading based on a transmission loss experiment we compute mean broadband source levels for the ship population of 173 ± 7 dB re 1 µPa 1 m without accounting for frequency-dependent absorption. Mean ship speed was 7.3 ± 2.0 m/s (14.1 ± 3.9 knots). Most ship classes show a linear relationship between source level and speed with a slope near +2 dB per m/s (+1 dB/knot). Spectrum, 1/12-octave, and 1/3-octave source levels for the whole population have median values that are comparable to previous measurements and models at most frequencies, but for select studies may be relatively low below 200 Hz and high above 20,000 Hz. Median source spectrum levels peak near 50 Hz for all 12 ship classes, have a maximum of 159 dB re 1 µPa2/Hz @ 1 m for container ships, and vary between classes. Below 200 Hz, the class-specific median spectrum levels bifurcate with large commercial ships grouping as higher power noise sources. Within all ship classes spectrum levels vary more at low frequencies than at high frequencies, and the degree of variability is almost halved for classes that have smaller speed standard deviations. This is the first study to present source spectra for populations of different ship classes operating in coastal habitats, including at higher frequencies used by killer whales for both communication and echolocation. PMID:27004149

Relationships between starch synthase I and branching enzyme isozymes determined using double mutant rice lines

PubMed Central

2014-01-01

Background Starch is the most important carbohydrate in plant storage tissues. Multiple isozymes in at least four enzyme classes are involved in starch biosynthesis. Some of these isozymes are thought to interact and form complexes for efficient starch biosynthesis. Of these enzyme classes, starch synthases (SSs) and branching enzymes (BEs) play particularly central roles. Results We generated double mutant lines (ss1/be1 and ss1 L /be2b) between SSI (the largest component of total soluble SS activity) and BEI or BEIIb (major BEs in developing rice endosperm) to explore the relationships among these isozymes. The seed weight of ss1/be1 was comparable to that of wild type, although most ss1/be2b seeds were sterile and no double recessive plants were obtained. The seed weight of the double recessive mutant line ss1 L /be2b, derived from the leaky ss1 mutant (ss1 L ) and be2b, was higher than that of the single be2b mutant. Analyses of the chain-length distribution of amylopectin in ss1/be1 endosperm revealed additive effects of SSI and BEI on amylopectin structure. Chain-length analysis indicated that the BEIIb deficiency significantly reduced the ratio of short chains in amylopectin of ss1 L /be2b. The amylose content of endosperm starch of ss1/be1 and ss1 L /be2b was almost the same as that of wild type, whereas the endosperm starch of be2b contained more amylose than did that of wild type. SSI, BEI, and BEIIb deficiency also affected the extent of binding of other isozymes to starch granules. Conclusions Analysis of the chain-length distribution in amylopectin of the double mutant lines showed that SSI and BEI or BEIIb primarily function independently, and branching by BEIIb is followed by SSI chain elongation. The increased amylose content in be2b was because of reduced amylopectin biosynthesis; however, the lower SSI activity in this background may have enhanced amylopectin biosynthesis as a result of a correction of imbalance between the branching and elongation found in the single mutant. The fact that a deficiency of SSI, BEI, or BEIIb affected the affinity of other starch biosynthetic isozymes for the starch granule implies that there is a close interaction among SSI, BEI and BEIIb during amylopectin biosynthesis in rice endosperm. PMID:24670252

Relationships between starch synthase I and branching enzyme isozymes determined using double mutant rice lines.

PubMed

Abe, Natsuko; Asai, Hiroki; Yago, Hikari; Oitome, Naoko F; Itoh, Rumiko; Crofts, Naoko; Nakamura, Yasunori; Fujita, Naoko

2014-03-26

Starch is the most important carbohydrate in plant storage tissues. Multiple isozymes in at least four enzyme classes are involved in starch biosynthesis. Some of these isozymes are thought to interact and form complexes for efficient starch biosynthesis. Of these enzyme classes, starch synthases (SSs) and branching enzymes (BEs) play particularly central roles. We generated double mutant lines (ss1/be1 and ss1L/be2b) between SSI (the largest component of total soluble SS activity) and BEI or BEIIb (major BEs in developing rice endosperm) to explore the relationships among these isozymes. The seed weight of ss1/be1 was comparable to that of wild type, although most ss1/be2b seeds were sterile and no double recessive plants were obtained. The seed weight of the double recessive mutant line ss1L/be2b, derived from the leaky ss1 mutant (ss1L) and be2b, was higher than that of the single be2b mutant. Analyses of the chain-length distribution of amylopectin in ss1/be1 endosperm revealed additive effects of SSI and BEI on amylopectin structure. Chain-length analysis indicated that the BEIIb deficiency significantly reduced the ratio of short chains in amylopectin of ss1L/be2b. The amylose content of endosperm starch of ss1/be1 and ss1L/be2b was almost the same as that of wild type, whereas the endosperm starch of be2b contained more amylose than did that of wild type. SSI, BEI, and BEIIb deficiency also affected the extent of binding of other isozymes to starch granules. Analysis of the chain-length distribution in amylopectin of the double mutant lines showed that SSI and BEI or BEIIb primarily function independently, and branching by BEIIb is followed by SSI chain elongation. The increased amylose content in be2b was because of reduced amylopectin biosynthesis; however, the lower SSI activity in this background may have enhanced amylopectin biosynthesis as a result of a correction of imbalance between the branching and elongation found in the single mutant. The fact that a deficiency of SSI, BEI, or BEIIb affected the affinity of other starch biosynthetic isozymes for the starch granule implies that there is a close interaction among SSI, BEI and BEIIb during amylopectin biosynthesis in rice endosperm.

The Escherichia coli phylogenetic group B2 with integrons prevails in childhood recurrent urinary tract infections.

PubMed

Kõljalg, Siiri; Truusalu, Kai; Stsepetova, Jelena; Pai, Kristiine; Vainumäe, Inga; Sepp, Epp; Mikelsaar, Marika

2014-05-01

The aim of our study was to characterize the phylogenetic groups of Escherichia coli, antibiotic resistance, and containment of class 1 integrons in the first attack of pyelonephritis and in subsequent recurrences in young children. Altogether, 89 urine E. coli isolates from 41 children with urinary tract infection (UTI) were studied for prevalence and persistence of phylogenetic groups by pulsed-field gel electrophoresis (PFGE), antibacterial resistance by minimal inhibitory concentrations (MIC) and class 1 integrons by PCR. Phylogenetic group B2 was most common (57%), followed by D (20%), A (18%) and B1 (5%). Overall resistance to betalactams was 61%, trimethoprim-sulfamethoxazole 28%, and was not associated with phylogenetic groups. According to PFGE, the same clonal strain persisted in 77% of patients. The persistence was detected most often in phylogenetic group B2 (70%). Phylogenetic group B2 more often contained class 1 integrons than group A. Integron positive strains had higher MIC values of cefuroxime, cefotaxime, and gentamicin. In conclusion, phylogenetic group B2 was the most common cause of the first episode of pyelonephritis, as well as in case of the persistence of the same strain and contained frequently class 1 integrons in childhood recurrent UTI. An overall frequent betalactam resistance was equally distributed among phylogenetic groups. © 2013 APMIS. Published by John Wiley & Sons Ltd.

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus.

PubMed

Liu, Q; Bu, D-F; Li, D; Zhu, X-J

2008-03-01

Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.

Germinal center hypoxia potentiates immunoglobulin class switch recombination

PubMed Central

Abbott, Robert K.; Thayer, Molly; Labuda, Jasmine; Silva, Murillo; Philbrook, Phaethon; Cain, Derek W.; Kojima, Hidefumi; Hatfield, Stephen; Sethumadhavan, Shalini; Ohta, Akio; Reinherz, Ellis L.; Kelsoe, Garnett; Sitkovsky, Michail

2016-01-01

Germinal centers (GCs) are anatomic sites where B cells undergo secondary diversification to produce high affinity, class switched antibodies. We hypothesized that proliferating B cells in GCs create a hypoxic microenvironment that governs their further differentiation. Using molecular markers, we found GCs to be predominantly hypoxic. Compared to normoxia (21% O2), hypoxic culture conditions (1% O2) in vitro accelerated class switching and plasma cell formation and enhanced expression of GL-7 on B and CD4+ T cells. Reversal of GC hypoxia in vivo by breathing 60% O2 during immunization resulted in reduced frequencies of GC B cells, T follicular helper (TFH) cells and plasmacytes, as well as lower expression of ICOS on TFH. Importantly, this reversal of GC hypoxia decreased antigen-specific serum IgG1 and reduced the frequency of IgG1+ B cells within the antigen specific GC. Taken together, these observations reveal a critical role for hypoxia in GC B cell differentiation. PMID:27798169

Impact of surface disinfection and sterile draping of furniture on room air quality in a cardiac procedure room with a ventilation and air-conditioning system (extrusion airflow, cleanroom class 1b (DIN 1946-4)).

PubMed

Below, Harald; Ryll, Sylvia; Empen, Klaus; Dornquast, Tina; Felix, Stefan; Rosenau, Heike; Kramer, Sebastian; Kramer, Axel

2010-09-21

In a cardiac procedure room, ventilated by a ventilation and air-conditioning system with turbulent mixed airflow, a protection zone in the operating area could be defined through visualization of airflows. Within this protection zone, no turbulence was detectable in the room air.Under the given conditions, disinfection of all surfaces including all furniture and equipment after the last operation and subsequent draping of furniture and all equipment that could not be removed from the room with sterile surgical drapes improved the indoor room air quality from cleanroom class C to cleanroom class B. This also allows procedures with elevated requirements to be performed in room class 1b.

Herpes B Virus, Macacine Herpesvirus 1, Breaks Simplex Virus Tradition via Major Histocompatibility Complex Class I Expression in Cells from Human and Macaque Hosts

PubMed Central

Vasireddi, Mugdha

2012-01-01

B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8+ T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are representative of foreign and natural host initial target cells of B virus. Our results show <20% downregulation of surface MHC class I molecules in either type of host cells infected with B virus, which is statistically insignificantly different from that observed in uninfected cells. We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA-G, involved in NK cell inhibition. Our results showed significant upregulation of HLA-E and HLA-G in host cells infected with B virus relative to the amounts observed in other herpesvirus-infected cells. These results suggest that B virus-infected cell surfaces maintain normal levels of MHC class Ia molecules, a finding unique among simplex viruses. This is a unique divergence in immune evasion for B virus, which, unlike human simplex viruses, does not inhibit the transport of peptides for loading onto MHC class Ia molecules because B virus ICP47 lacks a transporter-associated protein binding domain. The fact that MHC class Ib molecules were significantly upregulated has additional implications for host-pathogen interactions. PMID:22973043

Self-resistance in Streptomyces, with Special Reference to β-Lactam Antibiotics.

PubMed

Ogawara, Hiroshi

2016-05-10

Antibiotic resistance is one of the most serious public health problems. Among bacterial resistance, β-lactam antibiotic resistance is the most prevailing and threatening area. Antibiotic resistance is thought to originate in antibiotic-producing bacteria such as Streptomyces. In this review, β-lactamases and penicillin-binding proteins (PBPs) in Streptomyces are explored mainly by phylogenetic analyses from the viewpoint of self-resistance. Although PBPs are more important than β-lactamases in self-resistance, phylogenetically diverse β-lactamases exist in Streptomyces. While class A β-lactamases are mostly detected in their enzyme activity, over two to five times more classes B and C β-lactamase genes are identified at the whole genomic level. These genes can subsequently be transferred to pathogenic bacteria. As for PBPs, two pairs of low affinity PBPs protect Streptomyces from the attack of self-producing and other environmental β-lactam antibiotics. PBPs with PASTA domains are detectable only in class A PBPs in Actinobacteria with the exception of Streptomyces. None of the Streptomyces has PBPs with PASTA domains. However, one of class B PBPs without PASTA domain and a serine/threonine protein kinase with four PASTA domains are located in adjacent positions in most Streptomyces. These class B type PBPs are involved in the spore wall synthesizing complex and probably in self-resistance. Lastly, this paper emphasizes that the resistance mechanisms in Streptomyces are very hard to deal with, despite great efforts in finding new antibiotics.

Feather conditions and clinical scores as indicators of broilers welfare at the slaughterhouse.

PubMed

Saraiva, S; Saraiva, C; Stilwell, G

2016-08-01

The objective of this study was to evaluate the welfare of 64 different broiler farms on the basis of feather conditions and clinical scores measures collected at the slaughterhouse. A 3-point scale (0, 1 or 2) was used to classify dirty feathers, footpad dermatitis and hock burns measures, and a 2-point scale (present or absent) was used to classify breast burns, breast blisters and breast ulcer measures. Flocks were allocated into three body weight (BW) classes (A, B, C): class A (light) ≥1.43 and ≤1.68kg, class B (medium) ≥1.69 and ≤1.93kg; class C (heavy) ≥1.94 and ≤2.41kg. The absence of hock burns was more common in class A, while mild hock burns was more common in class B flocks. Breast ulcer was observed in class C flocks. The association observed for mild hock burns, breast burns and severe footpad dermatitis can indicate a simultaneous occurrence of these painful lesions. Very dirty feathers and severe footpad dermatitis relationship suggest litter humidity to be the common underlying cause. In conclusion, it was shown that clinical indicators can be used at the slaughterhouse to identify welfare problems. In the studied flocks, footpad dermatitis, feather conditions and hock burns were the main restrictions for good welfare and should be considered significant welfare indicators of the on-farm rearing conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

12 CFR 931.1 - Classes of capital stock.

Code of Federal Regulations, 2014 CFR

2014-01-01

... par value as determined by the board of directors of the Bank and stated in the Bank's capital plan; (2) Be issued, redeemed, and repurchased only at its stated par value; and (3) Be redeemable in cash only on six-months written notice to the Bank. (b) Class B stock, which shall: (1) Have a par value as...

12 CFR 931.1 - Classes of capital stock.

Code of Federal Regulations, 2013 CFR

2013-01-01

... par value as determined by the board of directors of the Bank and stated in the Bank's capital plan; (2) Be issued, redeemed, and repurchased only at its stated par value; and (3) Be redeemable in cash only on six-months written notice to the Bank. (b) Class B stock, which shall: (1) Have a par value as...

12 CFR 931.1 - Classes of capital stock.

Code of Federal Regulations, 2012 CFR

2012-01-01

... par value as determined by the board of directors of the Bank and stated in the Bank's capital plan; (2) Be issued, redeemed, and repurchased only at its stated par value; and (3) Be redeemable in cash only on six-months written notice to the Bank. (b) Class B stock, which shall: (1) Have a par value as...

26 CFR 1.652(b)-2 - Allocation of income items.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) INCOME TAXES Trusts Which Distribute Current Income Only § 1.652(b)-2 Allocation of income items... distributable net income of the trust (as defined in section 643(a)) as the total of each class bears to such distributable net income, unless the terms of the trust specifically allocate different classes of income to...

26 CFR 1.883-2T - Treatment of publicly-traded corporations (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... shareholders, as defined in § 1.883-4(b)(1); (B) The total percentage of the value of the shares owned... outstanding shares in that class of stock as of the close of the taxable year, and the value of each class of stock in relation to the total value of all the corporation's shares outstanding as of the close of the...

Complex MHC class I gene transcription profiles and their functional impact in orangutans

PubMed Central

de Groot, Natasja G.; Heijmans, Corrine M.C.; van der Wiel, Marit K.H.; Blokhuis, Jeroen H.; Mulder, Arend; Guethlein, Lisbeth A.; Doxiadis, Gaby G.M.; Claas, Frans H.J.; Parham, Peter; Bontrop, Ronald E.

2015-01-01

MHC haplotypes of humans and the African great ape species have one copy of the MHC-A, -B, and -C genes. In contrast, MHC haplotypes of orangutans, the Asian great ape species, exhibit variation in the number of gene copies. An in-depth analysis of the MHC class I gene repertoire in the two orangutan species, Pongo abelii and Pongo pygmaeus, is presented here. This analysis involved Sanger and next-generation sequencing methodologies, revealing diverse and complicated transcription profiles for orangutan MHC-A, -B, and -C. Thirty-five previously unreported MHC class I alleles are described. The data demonstrate that each orangutan MHC haplotype has one copy of the MHC-A gene, and that the MHC-B region has been subject to duplication, giving rise to at least three MHC-B genes. The MHC-B*03 and -B*08 lineages of alleles each account for a separate MHC-B gene. All MHC-B*08 allotypes have the C1-epitope motif recognized by KIR. At least one other MHC-B gene is present, pointing to MHC-B alleles that are not B*03 or B*08. The MHC-C gene is present only on some haplotypes, and each MHC-C allotype has the C1-epitope. The transcription profiles demonstrate that MHC-A alleles are highly transcribed, whereas MHC-C alleles, when present, are transcribed at very low levels. The MHC-B alleles are transcribed to a variable extent and over a wide range. For those orangutan MHC class I allotypes that are detected by human monoclonal anti-HLA class I antibodies, the level of cell-surface expression of proteins correlates with the level of transcription of the allele. PMID:26685209

An overview of the kinetic parameters of class B beta-lactamases.

PubMed Central

Felici, A; Amicosante, G; Oratore, A; Strom, R; Ledent, P; Joris, B; Fanuel, L; Frère, J M

1993-01-01

The catalytic properties of three class B beta-lactamases (from Pseudomonas maltophilia, Aeromonas hydrophila and Bacillus cereus) were studied and compared with those of the Bacteroides fragilis enzyme. The A. hydrophila beta-lactamase exhibited a unique specificity profile and could be considered as a rather specific 'carbapenemase'. No relationships were found between sequence similarities and catalytic properties. The problem of the repartition of class B beta-lactamases into sub-classes is discussed. Improved purification methods were devised for the P. maltophilia and A. hydrophila beta-lactamases including, for the latter enzyme, a very efficient affinity chromatography step on a Zn(2+)-chelate column. Images Figure 1 PMID:8471035

Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules.

PubMed

Hilton, H G; Parham, P

2013-04-01

Monoclonal antibodies with specificity for human leukocyte antigen (HLA) class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing three to six HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with 1 of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 not only exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1 µg/ml), PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50 µg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23 and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets. © 2013 John Wiley & Sons A/S.

B1-Metallo-beta-Lactamases: Where do we stand?

PubMed Central

Mojica, Maria F.; Bonomo, Robert A.; Fast, Walter

2015-01-01

Metallo-beta-Lactamases (MBLs) are class B β-lactamases that hydrolyze almost all clinically-available β-lactam antibiotics. MBLs feature the distinctive αβ/βα sandwich fold of the metallo-hydrolase / oxidoreductase superfamily and possess a shallow active-site groove containing one or two divalent zinc ions, flanked by flexible loops. According to sequence identity and zinc ion dependence, MBLs are classified into three subclasses (B1, B2 and B3), of which the B1 subclass enzymes have emerged as the most clinically significant. Differences among the active site architectures, the nature of zinc ligands, and the catalytic mechanisms have limited the development of a common inhibitor. In this review, we will describe the molecular epidemiology and structural studies of the most prominent representatives of class B1 MBLs (NDM-1, IMP-1 and VIM-2) and describe the implications for inhibitor design to counter this growing clinical threat. PMID:26424398

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

Lewis, M.S.

The Barnwell Waste Management Facility (BWMF) is scheduled to restrict access to waste generators outside of the Atlantic Compact (SC, CT, NJ) on July 1, 2008. South Carolina, authorized under the Low-Level Waste Policy Act of 1980 and Amendments Act of 1985, and in agreement with the other Atlantic Compact states, will only accept Class A, B, and C low-level radioactive waste (LLRW) generated within compact. For many years, the BWMF has been the only LLRW disposal facility to accept Class B and C waste from LLRW generators throughout the country, except those that have access to the Northwest Compactmore » Site. Many Class B/C waste generators consider this to be a national crisis situation requiring interim or possible permanent storage, changes in operation, significant cost impacts, and/or elimination of services, especially in the health care and non-power generation industries. With proper in-house waste management practices and utilization of commercial processor services, a national crisis can be avoided, although some generators with specific waste forms or radionuclides will remain without options. In summary: It is unknown what the future will bring for commercial LLRW disposal. Could the anticipated post Barnwell Class B/C crisis be avoided by any of the following? - Barnwell Site remains open for the nation's commercial Class B/C waste; - Richland Site opens back up to the nation for commercial Class B/C waste; - Texas Site opens up to the nation for commercial Class B/C waste; - Federal Government intervenes by keeping a commercial Class B/C site open for the nation's commercial Class B/C waste; - Federal Government makes a DOE site available for commercial Class B/C waste; - Federal Government revisits the LLRW Policy Act of 1980 and Amendments Act of 1985. Without a future LLRW site capable of accepting Class B/C currently on the horizon, commercial LLRW generators are faced with waste volume elimination, reduction, or storage. With proper in-house waste management practices, utilization of commercial processor services and regulatory relief, a national crisis can be avoided. Waste volumes for storage can be reduced to as little as 10% of the current Class B/C volume. Although a national LLRW crisis can be avoided, some generators with specific waste forms or radionuclides will have a significant financial and/or operational impact due to a lack of commercial LLRW management options. (authors)« less

Exploring the Role of Coliform Bacteria in Class 1 Integron Carriage and Biofilm Formation During Drinking Water Treatment.

PubMed

Farkas, Anca; Crăciunaş, Cornelia; Chiriac, Cecilia; Szekeres, Edina; Coman, Cristian; Butiuc-Keul, Anca

2016-11-01

This study investigates the role of coliforms in the carriage of class 1 integron and biocide resistance genes in a drinking water treatment plant and explores the relationship between the carriage of such genes and the biofouling abilities of the strain. The high incidence of class 1 integron and biocide resistance genes (33.3 % of the isolates) highlights the inherent risk of genetic contamination posed by coliform populations during drinking water treatment. The association between the presence of intI1 gene and qac gene cassettes, especially qacH, was greater in biofilm cells. In coliforms recovered from biofilms, a higher frequency of class 1 integron elements and higher diversity of genetic patterns occurred, compared to planktonic cells. The coliform isolates under the study proved to mostly carry non-classical class 1 integrons lacking the typical qacEΔ1/sul1 genes or a complete tni module, but bearing the qacH gene. No link was found between the carriage of integron genes and the biofouling degree of the strain, neither in aerobic or in anaerobic conditions. Coliform bacteria isolated from established biofilms rather adhere in oxygen depleted environments, while the colonization ability of planktonic cells is not significantly affected by oxygen availability.

Simultaneous multicolour optical and near-IR transit photometry of GJ 1214b with SOFIA

NASA Astrophysics Data System (ADS)

Angerhausen, D.; Dreyer, C.; Placek, B.; Csizmadia, Sz.; Eigmüller, Ph.; Godolt, M.; Kitzmann, D.; Mallonn, M.; Becklin, E. E.; Collins, P.; Dunham, E. W.; Grenfell, J. L.; Hamilton, R. T.; Kabath, P.; Logsdon, S. E.; Mandell, A.; Mandushev, G.; McElwain, M.; McLean, I. S.; Pfueller, E.; Rauer, H.; Savage, M.; Shenoy, S.; Vacca, W. D.; Van Cleve, J. E.; Wiedemann, M.; Wolf, J.

2017-12-01

Context. The benchmark exoplanet GJ 1214b is one of the best studied transiting planets in the transition zone between rocky Earth-sized planets and gas or ice giants. This class of super-Earth or mini-Neptune planets is unknown in our solar system, yet is one of the most frequently detected classes of exoplanets. Understanding the transition from rocky to gaseous planets is a crucial step in the exploration of extrasolar planetary systems, in particular with regard to the potential habitability of this class of planets. Aims: GJ 1214b has already been studied in detail from various platforms at many different wavelengths. Our airborne observations with the Stratospheric Observatory for Infrared Astronomy (SOFIA) add information in the Paschen-α cont. 1.9 μm infrared wavelength band, which is not accessible by any other current ground- or space-based instrument due to telluric absorption or limited spectral coverage. Methods: We used FLIPO, the combination of the High-speed Imaging Photometer for Occultations (HIPO) and the First Light Infrared TEst CAMera (FLITECAM) and the Focal Plane Imager (FPI+) on SOFIA to comprehensively analyse the transmission signal of the possible water-world GJ 1214b through photometric observations during transit in three optical and one infrared channels. Results: We present four simultaneous light curves and corresponding transit depths in three optical and one infrared channel, which we compare to previous observations and current synthetic atmospheric models of GJ 1214b. The final precision in transit depth is between 1.5 and 2.5 times the theoretical photon noise limit, not sensitive enough to constrain the theoretical models any better than previous observations. This is the first exoplanet observation with SOFIA that uses its full set of instruments available to exoplanet spectrophotometry. Therefore we use these results to evaluate SOFIA's potential in this field and suggest future improvements. Tables of the lightcurve data are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/608/A120

Elementary and Junior High School Teachers' Promotion of Self-Determination in Taiwan

ERIC Educational Resources Information Center

Chao, Pen-Chiang; Chou, Yu-Chi

2017-01-01

The purpose of this study was to conduct a national survey, aiming to (a)explore how self-determination instruction is implemented by elementary and junior high school teachers; (b)examine the frequency with which the components of self-determination are taught; and (c)investigate whether teachers' gender, class setting, and teaching experience…

Three on Three: A Tale for Business Ethics Classes

ERIC Educational Resources Information Center

VanSandt, Craig V.

2005-01-01

This article presents a novel approach to teaching business ethics to college students by relying on well-known aids to learning new, complex, and/or abstract material. The primary purpose of this article is threefold: (a) to explore some of the reasons why learning the basics of moral philosophies is relatively difficult for many students; (b) to…

Interaction of Body Mass Index on the Association Between N-Terminal-Pro-b-Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Bhatt, Ankeet S; Cooper, Lauren B; Ambrosy, Andrew P; Clare, Robert M; Coles, Adrian; Joyce, Emer; Krishnamoorthy, Arun; Butler, Javed; Felker, G Michael; Ezekowitz, Justin A; Armstrong, Paul W; Hernandez, Adrian F; O'Connor, Christopher M; Mentz, Robert J

2018-02-03

Higher body mass index (BMI) is associated with lower circulating levels of N-terminal-pro-b-type natriuretic peptide (NT-proBNP). The Interaction between BMI and NT-proBNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. A total of 686 patients from the biomarker substudy of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT-proBNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI <30 kg/m 2 , Class I obesity: BMI 30-34.9 kg/m 2 , Class II obesity BMI 35-39.9 kg/m 2 , and Class III obesity BMI ≥40 kg/m 2 ). We assessed baseline characteristics and 30- and 180-day outcomes by BMI class and explored the interaction between BMI and NT-proBNP for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female. NT-proBNP levels were inversely correlated with BMI ( P <0.001). Higher NT-proBNP levels were associated with higher 180-day mortality (adjusted hazard ratio for each doubling of NT-proBNP, 1.40; 95% confidence interval, 1.16, 1.71; P <0.001), but not 30-day outcomes. The effect of NT-proBNP on 180-day death was not modified by BMI class (interaction P =0.24). The prognostic value of NT-proBNP was not modified by BMI in this acute heart failure population. NT-proBNP remains a useful prognostic indicator of long-term mortality in acute heart failure even in the obese patient. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Heterotopic expression of class B floral homeotic genes supports a modified ABC model for tulip (Tulipa gesneriana).

PubMed

Kanno, Akira; Saeki, Hiroshi; Kameya, Toshiaki; Saedler, Heinz; Theissen, Günter

2003-07-01

In higher eudicotyledonous angiosperms the floral organs are typically arranged in four different whorls, containing sepals, petals, stamens and carpels. According to the ABC model, the identity of these organs is specified by floral homeotic genes of class A, A+B, B+C and C, respectively. In contrast to the sepal and petal whorls of eudicots, the perianths of many plants from the Liliaceae family have two outer whorls of almost identical petaloid organs, called tepals. To explain the Liliaceae flower morphology, van Tunen et al. (1993) proposed a modified ABC model, exemplified with tulip. According to this model, class B genes are not only expressed in whorls 2 and 3, but also in whorl 1. Thus the organs of both whorls 1 and 2 express class A plus class B genes and, therefore, get the same petaloid identity. To test this modified ABC model we have cloned and characterized putative class B genes from tulip. Two DEF- and one GLO-like gene were identified, named TGDEFA, TGDEFB and TGGLO. Northern hybridization analysis showed that all of these genes are expressed in whorls 1, 2 and 3 (outer and inner tepals and stamens), thus corroborating the modified ABC model. In addition, these experiments demonstrated that TGGLO is also weakly expressed in carpels, leaves, stems and bracts. Gel retardation assays revealed that TGGLO alone binds to DNA as a homodimer. In contrast, TGDEFA and TGDEFB cannot homodimerize, but make heterodimers with PI. Homodimerization of GLO-like protein has also been reported for lily, suggesting that this phenomenon is conserved within Liliaceae plants or even monocot species.

Impact of surface disinfection and sterile draping of furniture on room air quality in a cardiac procedure room with a ventilation and air-conditioning system (extrusion airflow, cleanroom class 1b (DIN 1946-4))

PubMed Central

Below, Harald; Ryll, Sylvia; Empen, Klaus; Dornquast, Tina; Felix, Stefan; Rosenau, Heike; Kramer, Sebastian; Kramer, Axel

2010-01-01

In a cardiac procedure room, ventilated by a ventilation and air-conditioning system with turbulent mixed airflow, a protection zone in the operating area could be defined through visualization of airflows. Within this protection zone, no turbulence was detectable in the room air. Under the given conditions, disinfection of all surfaces including all furniture and equipment after the last operation and subsequent draping of furniture and all equipment that could not be removed from the room with sterile surgical drapes improved the indoor room air quality from cleanroom class C to cleanroom class B. This also allows procedures with elevated requirements to be performed in room class 1b. PMID:20941336

HLA class I-mediated control of HIV-1 in the Japanese population, in which the protective HLA-B*57 and HLA-B*27 alleles are absent.

PubMed

Naruto, Takuya; Gatanaga, Hiroyuki; Nelson, George; Sakai, Keiko; Carrington, Mary; Oka, Shinichi; Takiguchi, Masafumi

2012-10-01

We investigated the effect of HLA class I alleles on clinical parameters for HIV-1 disease progression in the Japanese population, where two strongly protective alleles, HLA-B*57 and HLA-B*27, are virtually nonexistent. HLA-B alleles showed a dominant role, primarily through HLA-B*67:01 and the HLA-B*52:01-C*12:02 haplotype. Neither a rare-allele nor a heterozygote advantage was found, suggesting that the effect of HLA alleles in the Japanese population is either different from those observed in Africans and Caucasians or undetectable due to limited power.

HLA Class I-Mediated Control of HIV-1 in the Japanese Population, in Which the Protective HLA-B*57 and HLA-B*27 Alleles Are Absent

PubMed Central

Naruto, Takuya; Gatanaga, Hiroyuki; Nelson, George; Sakai, Keiko; Carrington, Mary; Oka, Shinichi

2012-01-01

We investigated the effect of HLA class I alleles on clinical parameters for HIV-1 disease progression in the Japanese population, where two strongly protective alleles, HLA-B*57 and HLA-B*27, are virtually nonexistent. HLA-B alleles showed a dominant role, primarily through HLA-B*67:01 and the HLA-B*52:01-C*12:02 haplotype. Neither a rare-allele nor a heterozygote advantage was found, suggesting that the effect of HLA alleles in the Japanese population is either different from those observed in Africans and Caucasians or undetectable due to limited power. PMID:22811530

A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b.

PubMed

Zeng, Li; Sullivan, Lucy C; Vivian, Julian P; Walpole, Nicholas G; Harpur, Christopher M; Rossjohn, Jamie; Clements, Craig S; Brooks, Andrew G

2012-01-01

The primary function of the monomorphic MHC class Ib molecule Qa-1(b) is to present peptides derived from the leader sequences of other MHC class I molecules for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas the mode of peptide presentation by its ortholog HLA-E, and subsequent recognition by CD94-NKG2A, is known, the molecular basis of Qa-1(b) function is unclear. We have assessed the interaction between Qa-1(b) and CD94-NKG2A and shown that they interact with an affinity of 17 μM. Furthermore, we have determined the structure of Qa-1(b) bound to the leader sequence peptide, Qdm (AMAPRTLLL), to a resolution of 1.9 Å and compared it with that of HLA-E. The crystal structure provided a basis for understanding the restricted peptide repertoire of Qa-1(b). Whereas the Qa-1(b-AMAPRTLLL) complex was similar to that of HLA-E, significant sequence and structural differences were observed between the respective Ag-binding clefts. However, the conformation of the Qdm peptide bound by Qa-1(b) was very similar to that of peptide bound to HLA-E. Although a number of conserved innate receptors can recognize heterologous ligands from other species, the structural differences between Qa-1(b) and HLA-E manifested in CD94-NKG2A ligand recognition being species specific despite similarities in peptide sequence and conformation. Collectively, our data illustrate the structural homology between Qa-1(b) and HLA-E and provide a structural basis for understanding peptide repertoire selection and the specificity of the interaction of Qa-1(b) with CD94-NKG2 receptors.

Diverse dissolution-recrystallization structural transformations and sequential Förster resonance energy transfer behavior of a luminescent porous Cd-MOF.

PubMed

Cao, Li-Hui; Li, Hai-Yang; Xu, Hong; Wei, Yong-Li; Zang, Shuang-Quan

2017-09-12

Metal-organic frameworks (MOFs) with light-harvesting building blocks provide an excellent platform to study energy transfer in networks with well-defined structures. Here, we report the synthesis, dissolution-recrystallization structural transformation (DRST) and the Förster resonance energy transfer (FRET) properties of a 2D microporous MOF {[Cd 2 (L 1 ) 3 (Hdabco) 2 ]·5DMAc·6H 2 O} n (Cd-MOF, 1). Complex 1 can be dissolved in water and three other products with different dimensions recrystallized from the aqueous solution under diverse reaction conditions were obtained. Due to the porosity and excellent blue luminescence properties of complex 1, we also studied the FRET process between 1 and guest dyes. Two distinct organic dye molecules viz., acridine orange (AO) and rhodamine B (RhB), are encapsulated in 1 which has honeycomb-type nanochannels, and their influence on fluorescence emission has also been studied. The microporous complex 1 in (AO + RhB)@1 serves as an energy funnel that harvests high energy excitation and channels it onto AO and then onto RhB. The steady-state fluorescence and fluorescence dynamics of emission reveal successfully the process of stepwise vectorial energy transfer. Therefore, MOFs could be a class of promising host materials to be further explored in the field of energy transfer between MOF-host and organic guests.

49 CFR 176.156 - Defective packages.

Code of Federal Regulations, 2010 CFR

2010-10-01

... packages. (a) No leaking, broken, or otherwise defective package containing Class 1 (explosive) materials.... (b) No Class 1 (explosive) material, which for any reason has deteriorated or undergone a change of...

Differential expression of MHC class II and B7 costimulatory molecules by microglia in rodent gliomas.

PubMed

Badie, Behnam; Bartley, Becky; Schartner, Jill

2002-12-01

To assess the immune function of microglia and macrophages in brain tumors, the expression of MHC class II and B7 costimulatory molecules in three rodent glioma models was examined. Microglia and macrophages, which accounted for 5-12% of total cells, expressed B7.1 and MHC class II molecules in the C6 and 9L tumors, but not RG2 gliomas. Interestingly, the expression of B7.1 and MHC class II molecules by microglia and macrophage was associated with an increase in the number of tumor-infiltrating lymphocytes in C6 and 9L tumors. B7.2 expression, which was present at low levels on microglia and macrophages in normal brain, did not significantly change in tumors. Interestingly, the expression of all three surface antigens increased after microglia were isolated from intracranial C6 tumors and cultured for a short period of time. We conclude that microglia immune activity may be suppressed in gliomas and directly correlates to the immunogenecity of experimental brain tumors.

Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors.

PubMed

Lavania, Dhruv; Dhingra, Anuradha; Grover, Anil

2018-06-01

Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.

Bandgap Engineering of Stable Lead-Free Oxide Double Perovskites for Photovoltaics.

PubMed

Sun, Qingde; Wang, Jing; Yin, Wan-Jian; Yan, Yanfa

2018-04-01

Despite the rapid progress in solar power conversion efficiency of archetype organic-inorganic hybrid perovskite CH 3 NH 3 PbI 3 -based solar cells, the long-term stability and toxicity of Pb remain the main challenges for the industrial deployment, leading to more uncertainties for global commercialization. The poor stabilities of CH 3 NH 3 PbI 3 -based solar cells may not only be attributed to the organic molecules but also the halides themself, most of which exhibit intrinsic instability under moisture and light. As an alternative, the possibility of oxide perovskites for photovoltaic applications is explored here. The class of lead-free stable oxide double perovskites A 2 M(III)M(V)O 6 (A = Ca, Sr, Ba; M(III) = Sb 3+ or Bi 3+ ; M(V) = V 5+ , Nb 5+ , or Ta 5+ ) is comprehensively explored with regard to their stability and their electronic and optical properties. Apart from the strong stability, this class of double perovskites exhibits direct bandgaps ranging from 0.3 to 3.8 eV. With proper B site alloying, the bandgap can be tuned within the range of 1.0-1.6 eV with optical absorptions as strong as CH 3 NH 3 PbI 3 , making them suitable for efficient single-junction thin-film solar cell application. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of four microbial Class II fructose 1,6-bisphosphate aldolase enzymes for use as biocatalysts.

PubMed

Labbé, Geneviève; de Groot, Sarah; Rasmusson, Timothy; Milojevic, Gorica; Dmitrienko, Gary I; Guillemette, J Guy

2011-12-01

Fructose 1,6-bisphosphate (FBP) aldolase has been used as biocatalyst in the synthesis of several pharmaceutical compounds such as monosaccharides and analogs. Is has been suggested that microbial metal-dependant Class II aldolases could be better industrial catalysts than mammalian Class I enzyme because of their greater stability. The Class II aldolases from four microbes were subcloned into the Escherichia coli vector pT7-7, expressed and purified to near homogeneity. The kinetic parameters, temperature stability, pH profile, and tolerance to organic solvents of the Class II enzymes were determined, and compared with the properties of the Class I aldolase from rabbit muscle. Contrary to results obtained previously with the E. coli Class II aldolase, which was reported to be more stable than the mammalian enzyme, other recombinant Class II aldolases were found to be generally less stable than the Class I enzyme, especially in the presence of organic solvents. Class II aldolase from Bacillus cereus showed higher temperature stability than the other enzymes tested, but only the Mycobacterium tuberculosis Class II aldolase had a stability comparable to the Class I mammalian enzyme under assay conditions. The turnover number of the recombinant M. tuberculosis and Magnaporthe grisea Class II type A aldolases was comparable or higher than that of the Class I enzyme. The recombinant B. cereus and Pseudomonas aeruginosa Class II type B aldolases had very low turnover numbers and low metal content, indicating that the E. coli overexpression system may not be suitable for the Class II type B aldolases from these microorganisms. Copyright © 2011 Elsevier Inc. All rights reserved.

21 CFR 876.1075 - Gastroenterology-urology biopsy instrument.

Code of Federal Regulations, 2013 CFR

2013-04-01

... biopsy instrument, gastro-urology biopsy needle and needle set, and nonelectric biopsy forceps. This... regulations. (b) Classification. (1) Class II (performance standards). (2) Class I for the biopsy forceps cover and the non-electric biopsy forceps. The devices subject to this paragraph (b)(2) are exempt from...

21 CFR 876.1075 - Gastroenterology-urology biopsy instrument.

Code of Federal Regulations, 2014 CFR

2014-04-01

... biopsy instrument, gastro-urology biopsy needle and needle set, and nonelectric biopsy forceps. This... regulations. (b) Classification. (1) Class II (performance standards). (2) Class I for the biopsy forceps cover and the non-electric biopsy forceps. The devices subject to this paragraph (b)(2) are exempt from...

21 CFR 876.1075 - Gastroenterology-urology biopsy instrument.

Code of Federal Regulations, 2012 CFR

2012-04-01

... biopsy instrument, gastro-urology biopsy needle and needle set, and nonelectric biopsy forceps. This... regulations. (b) Classification. (1) Class II (performance standards). (2) Class I for the biopsy forceps cover and the non-electric biopsy forceps. The devices subject to this paragraph (b)(2) are exempt from...

Laparoscopic splenectomy for patients with liver cirrhosis: Improvement of liver function in patients with Child-Pugh class B.

PubMed

Yamamoto, Naoki; Okano, Keiichi; Oshima, Minoru; Akamoto, Shitaro; Fujiwara, Masao; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Masaki, Tsutomu; Suzuki, Yasuyuki

2015-12-01

We aimed to assess the short-term outcomes of laparoscopic splenectomy (LS) and liver function at 1 year after splenectomy in the patients with liver cirrhosis. Forty-five patients with liver cirrhosis and hypersplenism underwent LS. We reviewed electronic medical records regarding the liver functional reserve, the etiology of liver cirrhosis, and the presence of hepatocellular carcinoma and esophago-gastric varices. Prospectively collected data of perioperative variables, postoperative complications, and long-term liver function were analyzed. Forty-five patients had a chronic liver disease classified into Child-Pugh classes (A/B/C: 23/20/2). The etiologies of disease were hepatitis C virus infection in 34 patients, hepatitis B virus infection in 4, and others in 7. Fourteen patients underwent procedures in addition to LS, including hepatectomy (n = 7) and devascularization for esophagogastric varices (n = 8). Postoperative complications occurred in 11 patients (24%). Neither postoperative liver failure nor in-hospital mortality occurred. White blood cell and platelet counts determined 7 days, 1 month, and 1 year after LS doubled or increased more than twice compared with the preoperative values (P < .001). One year after LS, patients who had been classified preoperatively into Child-Pugh class B had decreased total serum bilirubin levels (P = .03), and increased prothrombin activity (P = 003) and decreased Child-Pugh scores (P = .001). The Child-Pugh classifications improved in 14 of 18 patients (78%) who had Child-Pugh class B preoperatively. LS is a safe and feasible procedure for hypersplenism in patients with liver cirrhosis. In addition, LS most likely ameliorates liver function at 1 year after LS in patients with Child-Pugh class B liver cirrhosis. Copyright © 2015 Elsevier Inc. All rights reserved.

75 FR 57704 - Head Start Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... environment. The Committee recommended incorporating a practical classroom observation tool and effective... Classroom Assessment Scoring System Pre-K (CLASS: Pre-K) in the two most recent CLASS: Pre-K observations... (CLASS: Pre-K) in the two most recent CLASS: Pre-K observations. Paragraph (b)(1) as proposed cites...

NASA's Space Launch System: An Evolving Capability for Exploration

NASA Technical Reports Server (NTRS)

Creech, Stephen D.; Robinson, Kimberly F.

2016-01-01

Designed to meet the stringent requirements of human exploration missions into deep space and to Mars, NASA's Space Launch System (SLS) vehicle represents a unique new launch capability opening new opportunities for mission design. NASA is working to identify new ways to use SLS to enable new missions or mission profiles. In its initial Block 1 configuration, capable of launching 70 metric tons (t) to low Earth orbit (LEO), SLS is capable of not only propelling the Orion crew vehicle into cislunar space, but also delivering small satellites to deep space destinations. The evolved configurations of SLS, including both the 105 t Block 1B and the 130 t Block 2, offer opportunities for launching co-manifested payloads and a new class of secondary payloads with the Orion crew vehicle, and also offer the capability to carry 8.4- or 10-m payload fairings, larger than any contemporary launch vehicle, delivering unmatched mass-lift capability, payload volume, and C3.

Association between traditional clinical high-risk features and gene expression profile classification in uveal melanoma.

PubMed

Nguyen, Brandon T; Kim, Ryan S; Bretana, Maria E; Kegley, Eric; Schefler, Amy C

2018-02-01

To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD. Of the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class. In this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.

Latent classes of resilience and psychological response among only-child loss parents in China.

PubMed

Wang, An-Ni; Zhang, Wen; Zhang, Jing-Ping; Huang, Fei-Fei; Ye, Man; Yao, Shu-Yu; Luo, Yuan-Hui; Li, Zhi-Hua; Zhang, Jie; Su, Pan

2017-10-01

Only-child loss parents in China recently gained extensive attention as a newly defined social group. Resilience could be a probable solution out of the psychological dilemma. Using a sample of 185 only-child loss people, this study employed latent class analysis (a) to explore whether different classes of resilience could be identified, (b) to determine socio-demographic characteristics of each class, and (c) to compare the depression and the subjective well-being of each class. The results supported a three-class solution, defined as 'high tenacity-strength but moderate optimism class', 'moderate resilience but low self-efficacy class' and 'low tenacity but moderate adaption-dependence class'. Parents with low income and medical insurance of low reimbursement type and without endowment insurance occupied more proportions in the latter two classes. The latter two classes also had a significant higher depression scores and lower subjective well-being scores than high tenacity-strength but moderate optimism class. Future work should care those socio-economically vulnerable bereaved parents, and an elastic economic assistance policy was needed. To develop targeted resilience interventions, the emphasis of high tenacity-strength but moderate optimism class should be the optimism. Moderate resilience but low self-efficacy class should be self-efficacy, and low tenacity but moderate adaption-dependence class should be tenacity. Copyright © 2016 John Wiley & Sons, Ltd.

Experimental tests of factorization in charmless nonleptonic two-body B decays

NASA Astrophysics Data System (ADS)

Ali, A.; Kramer, G.; Lü, Cai-Dian

1998-11-01

Using a theoretical framework based on the next-to-leading-order QCD-improved effective Hamiltonian and a factorization ansatz for the hadronic matrix elements of the four-quark operators, we reassess branching fractions in two-body nonleptonic decays B-->PP,PV,VV, involving the lowest-lying light pseudoscalar (P) and vector (V) mesons in the standard model. We work out the parametric dependence of the decay rates, making use of the currently available information on the weak mixing matrix elements, form factors, decay constants, and quark masses. Using the sensitivity of the decay rates on the effective number of colors, Nc, as a criterion of theoretical predictivity, we classify all the current-current (tree) and penguin transitions in five different classes. The recently measured charmless two-body B-->PP decays (B+-->K+η', B0-->K0η', B0-->K+π-, B+-->π+K0, and charge conjugates) are dominated by the Nc-stable QCD penguin transitions (class-IV transitions) and their estimates are consistent with the data. The measured charmless B-->PV (B+-->ωK+, B+-->ωh+) and B-->VV transition (B-->φK*), on the other hand, belong to the penguin (class-V) and tree (class-III) transitions. The class-V penguin transitions are Nc sensitive and/or involve large cancellations among competing amplitudes, making their decay rates in general more difficult to predict. Some of these transitions may also receive significant contributions from annihilation and/or final state interactions. We propose a number of tests of the factorization framework in terms of the ratios of branching ratios for some selected B-->h1h2 decays involving light hadrons h1 and h2, which depend only moderately on the form factors. We also propose a set of measurements to determine the effective coefficients of the current-current and QCD penguin operators. The potential impact of B-->h1h2 decays on the CKM phenomenology is emphasized by analyzing a number of decay rates in the factorization framework.

A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor.

PubMed

Gadd, Samantha; Huff, Vicki; Walz, Amy L; Ooms, Ariadne H A G; Armstrong, Amy E; Gerhard, Daniela S; Smith, Malcolm A; Auvil, Jaime M Guidry; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Dome, Jeffrey S; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Ross, Nicole; Gastier-Foster, Julie M; Arold, Stefan T; Perlman, Elizabeth J

2017-10-01

We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.

BONE MARROW–DERIVED DENDRITIC CELL PROGENITORS (NLDC 145+, MHC CLASS II+, B7–1dim, B7–2−) INDUCE ALLOANTIGEN-SPECIFIC HYPORESPONSIVENESS IN MURINE T LYMPHOCYTES12

PubMed Central

Lu, Lina; McCaslin, Delbert; Starzl, Thomas E.; Thomson, Angus W.

2010-01-01

The functional maturation of dendritic cells (DC) and other antigen-presenting cells is believed to reflect the upregulation of cell surface major histocompatibility complex (MHC) class II and other T cell co-stimulatory molecules, especially the CD28 ligands B7–1 (CD80) and B7–2 (CD86). In this study, we propagated cells exhibiting characteristics of DC precursors from the bone marrow (BM) of BIO mice (H-2b; I-A1) in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The methods used were similar to those employed previously to propagate DC progenitors from normal mouse liver. Cells expressing DC lineage markers (NLDC 145+, 33D1+ N418+) harvested from 8–10-day GM-CSF stimulated BM cell cultures were CD45+, heat-stable antigen+, CD54+, CD44+, MHC class II+, B7–1dim but B7–2− (costimulatory molecule-deficient). Supplementation of cultures with interleukin-4 (IL-4) in addition to GM-CSF however, resulted in marked upregulation of MHC class II and B7–2 expression. These latter cells exhibited potent allostimulatory activity in primary mixed leukocyte cultures. In contrast, the cells stimulated with GM-CSF alone were relatively weak stimulators and induced alloantigen-specific hyporesponsiveness in allogeneic T cells (C3H; H-2k; I-E+) detected upon re-stimulation in secondary MLR. This was associated with blockade of IL-2 production. Reactivity to third-party stimulators was intact. The hyporesponsiveness induced by the GM-CSF stimulated, costimulatory molecule-deficient cells was prevented by incorporation of anti-CD28 monoclonal antibody in the primary MLR and was reversed by addition of IL-2 to restimulated T cells. The findings show that MHC class II+ B7–2− cells with a DC precursor phenotype can induce alloantigen-specific hyporesponsiveness in vitro. Under the appropriate conditions, such costimulatory molecule-deficient cells could contribute to the induction of donor-specific unresponsiveness in vivo. PMID:8545887

Gender inequalities in health: exploring the contribution of living conditions in the intersection of social class.

PubMed

Malmusi, Davide; Vives, Alejandra; Benach, Joan; Borrell, Carme

2014-01-01

Women experience poorer health than men despite their longer life expectancy, due to a higher prevalence of non-fatal chronic illnesses. This paper aims to explore whether the unequal gender distribution of roles and resources can account for inequalities in general self-rated health (SRH) by gender, across social classes, in a Southern European population. Cross-sectional study of residents in Catalonia aged 25-64, using data from the 2006 population living conditions survey (n=5,817). Poisson regression models were used to calculate the fair/poor SRH prevalence ratio (PR) by gender and to estimate the contribution of variables assessing several dimensions of living conditions as the reduction in the PR after their inclusion in the model. Analyses were stratified by social class (non-manual and manual). SRH was poorer for women among both non-manual (PR 1.39, 95% CI 1.09-1.76) and manual social classes (PR 1.36, 95% CI 1.20-1.56). Adjustment for individual income alone eliminated the association between sex and SRH, especially among manual classes (PR 1.01, 95% CI 0.85-1.19; among non-manual 1.19, 0.92-1.54). The association was also reduced when adjusting by employment conditions among manual classes, and household material and economic situation, time in household chores and residential environment among non-manual classes. Gender inequalities in individual income appear to contribute largely to women's poorer health. Individual income may indicate the availability of economic resources, but also the history of access to the labour market and potentially the degree of independence and power within the household. Policies to facilitate women's labour market participation, to close the gender pay gap, or to raise non-contributory pensions may be helpful to improve women's health.

Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

PubMed

Chen, B P; Madrigal, A; Parham, P

1990-09-01

Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to lead exploration.

PubMed

Oza, Vibha; Ashwell, Susan; Brassil, Patrick; Breed, Jason; Deng, Chun; Ezhuthachan, Jay; Haye, Heather; Horn, Candice; Janetka, James; Lyne, Paul; Newcombe, Nicholas; Otterbien, Ludo; Pass, Martin; Read, Jon; Roswell, Sian; Su, Mei; Toader, Dorin; Yu, Dingwei; Yu, Yan; Valentine, Anna; Webborn, Peter; White, Ann; Zabludoff, Sonya; Zheng, Xiaolan

2010-09-01

Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described. Copyright 2010 Elsevier Ltd. All rights reserved.

A sharp lower bound for the sum of a sine series with convex coefficients

NASA Astrophysics Data System (ADS)

Solodov, A. P.

2016-12-01

The sum of a sine series g(\\mathbf b,x)=\\sumk=1^∞ b_k\\sin kx with coefficients forming a convex sequence \\mathbf b is known to be positive on the interval (0,π). Its values near zero are conventionally evaluated using the Salem function v(\\mathbf b,x)=x\\sumk=1m(x) kb_k, m(x)=[π/x]. In this paper it is proved that 2π-2v(\\mathbf b,x) is not a minorant for g(\\mathbf b,x). The modified Salem function v_0(\\mathbf b,x)=x\\bigl(\\sumk=1m(x)-1 kb_k+(1/2)m(x)bm(x)\\bigr) is shown to satisfy the lower bound g(\\mathbf b,x)>2π-2v_0(\\mathbf b,x) in some right neighbourhood of zero. This estimate is shown to be sharp on the class of convex sequences \\mathbf b. Moreover, the upper bound for g(\\mathbf b,x) is refined on the class of monotone sequences \\mathbf b. Bibliography: 11 titles.

49 CFR 238.315 - Class IA brake test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Class IA brake test. 238.315 Section 238.315... Requirements for Tier I Passenger Equipment § 238.315 Class IA brake test. (a) Except as provided in paragraph (b) of this section, either a Class I or a Class IA brake test shall be performed: (1) Prior to the...

Noise levels in fitness classes are still too high: evidence from 1997-1998 and 2009-2011.

PubMed

Beach, Elizabeth Francis; Nie, Valerie

2014-01-01

Fitness instructors routinely use high music volumes that may be harmful to hearing. This study assessed noise levels during 35 low-intensity and 65 high-intensity fitness classes in 1997-1998 and 2009-2011. Questionnaires examined instructors' and clients' preferred music volumes and whether they found loud music "stressful" or "motivating." Noise levels in 1997-1998 and 2009-2011 were similar, frequently exceeding 90 dB(A). Although noise levels in low-intensity classes dropped from 88.9 to 85.6 dB(A), they remained high for high-intensity classes, averaging 93.1 dB(A). In 2009-2011, instructors preferred significantly higher volumes than clients for high-intensity classes. In both time periods, about 85% of instructors found loud music motivating, whereas about one fifth of clients found it stressful. The results suggest that noise exposure from fitness classes, particularly high-intensity classes, continues to pose a potential risk to hearing.

A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides

PubMed Central

1994-01-01

Unlike the highly polymorphic major histocompatibility complex (MHC) class Ia molecules, which present a wide variety of peptides to T cells, it is generally assumed that the nonpolymorphic MHC class Ib molecules may have evolved to function as highly specialized receptors for the presentation of structurally unique peptides. However, a thorough biochemical analysis of one class Ib molecule, the soluble isoform of Qa-2 antigen (H-2SQ7b), has revealed that it binds a diverse array of structurally similar peptides derived from intracellular proteins in much the same manner as the classical antigen-presenting molecules. Specifically, we find that SQ7b molecules are heterodimers of heavy and light chains complexed with nonameric peptides in a 1:1:1 ratio. These peptides contain a conserved hydrophobic residue at the COOH terminus and a combination of one or more conserved residue(s) at P7 (histidine), P2 (glutamine/leucine), and/or P3 (leucine/asparagine) as anchors for binding SQ7b. 2 of 18 sequenced peptides matched cytosolic proteins (cofilin and L19 ribosomal protein), suggesting an intracellular source of the SQ7b ligands. Minimal estimates of the peptide repertoire revealed that at least 200 different naturally processed self-peptides can bind SQ7b molecules. Since Qa-2 molecules associate with a diverse array of peptides, we suggest that they function as effective presenting molecules of endogenously synthesized proteins like the class Ia molecules. PMID:8294869

47 CFR 73.99 - Presunrise service authorization (PSRA) and postsunset service authorization (PSSA).

Code of Federal Regulations, 2010 CFR

2010-10-01

... purposes. (b) Presunrise service authorizations (PSRA) permit: (1) Class D stations operating on Mexican... (PSSA) permit: (1) Class D stations located on Mexican, Bahamian, and Canadian priority Class A clear... basis and does not confer license rights. No request for such authority need be filed. However, stations...

Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns

PubMed Central

Tang, Deliang

2014-01-01

Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene–environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P. PMID:24177223

46 CFR 108.173 - Class I, Division 2 locations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... m (10 ft.) of a possible source of gas release; or (3) Within 1.5 m (5 ft.) of the boundaries of any...) Within 1.5 m (5 ft.) of a semi-enclosed Class I, Division 1 location indicated in § 108.171(b); or (2) Within 1.5 m (5 ft.) of a Class I, Division 1 space indicated in § 108.171(e). (d) A semi-enclosed area...

46 CFR 108.173 - Class I, Division 2 locations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... m (10 ft.) of a possible source of gas release; or (3) Within 1.5 m (5 ft.) of the boundaries of any...) Within 1.5 m (5 ft.) of a semi-enclosed Class I, Division 1 location indicated in § 108.171(b); or (2) Within 1.5 m (5 ft.) of a Class I, Division 1 space indicated in § 108.171(e). (d) A semi-enclosed area...

46 CFR 108.173 - Class I, Division 2 locations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... m (10 ft.) of a possible source of gas release; or (3) Within 1.5 m (5 ft.) of the boundaries of any...) Within 1.5 m (5 ft.) of a semi-enclosed Class I, Division 1 location indicated in § 108.171(b); or (2) Within 1.5 m (5 ft.) of a Class I, Division 1 space indicated in § 108.171(e). (d) A semi-enclosed area...

46 CFR 108.173 - Class I, Division 2 locations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... m (10 ft.) of a possible source of gas release; or (3) Within 1.5 m (5 ft.) of the boundaries of any...) Within 1.5 m (5 ft.) of a semi-enclosed Class I, Division 1 location indicated in § 108.171(b); or (2) Within 1.5 m (5 ft.) of a Class I, Division 1 space indicated in § 108.171(e). (d) A semi-enclosed area...

Distinct Immunoglobulin Class and Immunoglobulin G Subclass Patterns against Ganglioside GQ1b in Miller Fisher Syndrome following Different Types of Infection

PubMed Central

Schwerer, Beatrix; Neisser, Andrea; Bernheimer, Hanno

1999-01-01

We studied serum antibodies against gangliosides GQ1b and GM1 in 13 patients with Miller Fisher syndrome (MFS) and in 18 patients with Guillain-Barré syndrome (GBS) with cranial nerve involvement. Anti-GQ1b titers were elevated in all patients with MFS cases (immunoglobulin G [IgG] > IgA, IgM), and in 8 of the 18 with GBS. Lower frequencies of increased anti-GM1 titers were observed in MFS patients (3 of 13), as well as in GBS patients (5 of 18). During the course of MFS, anti-GQ1b titers of all Ig classes decreased within 3 weeks after onset. By contrast, anti-GM1 titers (mainly IgM) transiently increased during the course of MFS in five of six patients, suggesting a nonspecific secondary immune response. In patients with MFS following respiratory infections, IgG was the major anti-GQ1b Ig class (six of six patients) and IgG3 was the major subclass (five of six). In contrast, four of five patients with MFS following gastrointestinal infections showed predominance of anti-GQ1b IgA or IgM over IgG and predominance of the IgG2 subclass; anti-GQ1b IgG (IgG3) prevailed in one patient only. These distinct Ig patterns strongly suggest that different infections may trigger different mechanisms of anti-GQ1b production, such as via T-cell-dependent as opposed to T-cell-independent pathways. Thus, the origin of antibodies against GQ1b in MFS may be determined by the type of infectious agent that precipitates the disease. PMID:10225903

Heat shock factors HsfB1 and HsfB2b are involved in the regulation of Pdf1.2 expression and pathogen resistance in Arabidopsis.

PubMed

Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

2009-01-01

In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses.

Identification of broadly reactive epitopes targeting major glycoproteins of Herpes simplex virus (HSV) 1 and 2 - An immunoinformatics analysis.

PubMed

Chauhan, Varun; Goyal, Kapil; Singh, Mini P

2018-07-01

Infections due to both HSV-1 and HSV-2 constitute an enormous health burden worldwide. Development of vaccine against herpes infections is a WHO supported public health priority. The viral glycoproteins have always been the major hotspots for vaccine designing. The present study was aimed to identify the conserved T and B cell epitopes in the major glycoproteins of both HSV-1 and HSV-2 via rigorous computational approaches. Identification of promiscuous T cell epitopes is of utmost importance in vaccine designing as such epitopes are capable of binding to several allelic forms of HLA and could generate effective immune response in the host. The criteria designed for identification of T and B cell epitopes was that it should be conserved in both HSV-1 and 2, promiscuous, have high affinity towards HLA alleles, should be located on the surface of glycoproteins and not be present in the glycosylation sites. This study led to the identification of 17 HLA Class II and 26 HLA Class I T cell epitopes, 9 linear and some conformational B cell epitopes. The identified T cell epitopes were further subjected to molecular docking analysis to analyze their binding patterns. Altogether we have identified 4 most promising regions in glycoproteins (2-gB, 1-gD, 1-gH) of HSV-1 and 2 which are promiscuous to HLA Class II alleles and have overlapping HLA Class I and B cell epitopes, which could be very useful in generating both arms of immune response in the host i.e. adaptive as well as humoral immunity. Further the authors propose the cross-validation of the identified epitopes in experimental settings for confirming their immunogenicity to support the present findings. Copyright © 2018 Elsevier B.V. All rights reserved.

The NASA probe-class mission concept, CETUS (Cosmic Evolution Through Ultraviolet Spectroscopy)

NASA Astrophysics Data System (ADS)

Heap, Sara; Danchi, William; Burge, James; Dodson, Kelly; Hull, Anthony; Kendrick, Steven; McCandliss, Stephan; Mehle, Gregory; Purves, Lloyd; Sheikh, David; Valente, Martin; Woodruff, Robert A.

2017-09-01

We report on the early phases of a NASA-sponsored study of CETUS (Cosmic Evolution Through Ultraviolet Spectroscopy), a Probe-class mission concept. By definition, the full lifecycle cost of a Probe mission is greater than 400M (i.e. Explorer missions) and less than 1.00B ("Flagship" missions). The animating idea behind our study is that CETUS can help answer fundamental questions about galaxy evolution by carrying out a massive UV imaging and spectroscopic survey of galaxies and combining its findings with data obtained by other survey telescopes of the 2020's. The CETUS mission concept comprises a 1.5-m wide-field telescope and three scientific instruments: a near-UV multi-object slit spectrograph with a micro-shutter array as the slit device; a near-UV and far-UV camera with angular resolution of 0.42" (near-UV) or 0.55" (far-UV); and a near-UV or far-UV single-object spectrograph aimed at providing access to the UV after Hubble is gone. We describe the scientific rationale for CETUS and the telescope and instruments in their early design phase.

Overexpression of SIRT1 Protects Pancreatic β-Cells Against Cytokine Toxicity by Suppressing the Nuclear Factor-κB Signaling Pathway

PubMed Central

Lee, Ji-Hyun; Song, Mi-Young; Song, Eun-Kyung; Kim, Eun-Kyung; Moon, Woo Sung; Han, Myung-Kwan; Park, Jin-Woo; Kwon, Kang-Beom; Park, Byung-Hyun

2009-01-01

OBJECTIVE—SIRT1, a class III histone/protein deacetylase, is known to interfere with the nuclear factor-κB (NF-κB) signaling pathway and thereby has an anti-inflammatory function. Because of the central role of NF-κB in cytokine-mediated pancreatic β-cell damage, we postulated that SIRT1 might work in pancreatic β-cell damage models. RESEARCH DESIGN AND METHODS—RINm5F (RIN) cells or isolated rat islets were treated with interleukin-1β and interferon-γ. SIRT1 was activated by resveratrol, a pharmacological activator, or ectopic overexpression. The underlying mechanisms of SIRT1 against cytokine toxicity were further explored. RESULTS—Treatment of RIN cells with cytokines induced cell damage, and this damage was well correlated with the expression of the inducible form of nitric oxide (NO) synthase (iNOS) and NO production. However, SIRT1 overexpression completely prevented cytokine-mediated cytotoxicity, NO production, and iNOS expression. The molecular mechanism by which SIRT1 inhibits iNOS expression appeared to involve the inhibition of the NF-κB signaling pathway through deacetylation of p65. In addition, SIRT1 activation by either resveratrol or adenoviral-directed overexpression of SIRT1 could prevent cytokine toxicity and maintain normal insulin-secreting responses to glucose in isolated rat islets. CONCLUSIONS—This study will provide valuable information not only into the mechanisms underlying β-cell destruction but also into the regulation of SIRT1 as a possible target to attenuate cytokine-induced β-cell damage. PMID:19008341

Teaching Children with down Syndrome in the Early Years of School

ERIC Educational Resources Information Center

McFadden, Amanda; Tangen, Donna; Spooner-Lane, Rebecca; Mergler, Amanda

2017-01-01

We explored 3 general classroom teachers' experiences of including a child with Down syndrome in their early years classrooms. Located at 3 different Australian school settings, 1 teacher was the head of a Preparatory class, 1 was a Year 3 teacher, and the third was a teacher of a split Preparatory/Year 1 class. Interview data were drawn from a…

Travelling Hopefully: An Exploration of the Limited Possibilities for Level 1 Students in the English Further Education System

ERIC Educational Resources Information Center

Atkins, Liz

2008-01-01

This paper discusses the findings of a small-scale qualitative study exploring the aspirations and learning identities of three groups of Level 1 students in two English further education (FE) colleges. Emerging identities are explored in the context of classed and gendered dispositions and the educational positioning of the young people.…

An endophytic fungus from Azadirachta indica A. Juss. that produces azadirachtin.

PubMed

Kusari, Souvik; Verma, Vijay C; Lamshoeft, Marc; Spiteller, Michael

2012-03-01

Azadirachtin A and its structural analogues are a well-known class of natural insecticides having antifeedant and insect growth-regulating properties. These compounds are exclusive to the neem tree, Azadirachta indica A. Juss, from where they are currently sourced. Here we report for the first time, the isolation and characterization of a novel endophytic fungus from A. indica, which produces azadirachtin A and B in rich mycological medium (Sabouraud dextrose broth), under shake-flask fermentation conditions. The fungus was identified as Eupenicillium parvum by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Azadirachtin A and B were identified and quantified by LC-HRMS and LC-HRMS(2), and by comparison with the authentic reference standards. The biosynthesis of azadirachtin A and B by the cultured endophyte, which is also produced by the host neem plant, provides an exciting platform for further scientific exploration within both the ecological and biochemical contexts.

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix.

PubMed

Gilthorpe, Mark S; Harrison, Wendy J; Downing, Amy; Forman, David; West, Robert M

2011-03-01

Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs). Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared. Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs. A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.

Detection of class 1 and 2 integrons, extended-spectrum β-lactamases and qnr alleles in enterobacterial isolates from the digestive tract of Intensive Care Unit inpatients.

PubMed

Bado, Inés; Cordeiro, Nicolás F; Robino, Luciana; García-Fulgueiras, Virginia; Seija, Verónica; Bazet, Cristina; Gutkind, Gabriel; Ayala, Juan A; Vignoli, Rafael

2010-11-01

In this study, we searched for extended-spectrum β-lactamases (ESBLs), class 1 and 2 integrons, and qnrA, qnrB and qnrS genes in 56 oxyimino-cephalosporin and/or ciprofloxacin-resistant enterobacterial isolates obtained from the gastrointestinal tract of patients admitted in an Intensive Care Unit in Uruguay. ESBLs were detected in 11 isolates (6 CTX-M-2, 3 CTX-M-9, 1 CTX-M-15 and 1 PER-2). qnr genes and integrons were detected in 5 and 24 isolates, respectively. Eight different antibiotic resistance gene cassettes were found within six different genetic arrangements. Two types of complex class 1 integrons carrying insertion sequence ISCR1 were found, one showing bla(CTX-M-2)-orf3 and the other qnrA1-ampR. Ten of the thirteen isolates carrying class 2 integrons presented the element IS5 inserted between intI2 and dfrA1, whereas another class 2 integron lacked the internal stop codon usually present in intI2. This is the first report of the occurrence of qnrA, qnrB and bla(CTX-M-9) in Uruguay. Dissemination of the different groups of CTX-M enzymes (i.e. groups 1, 2 and 9) appears to be a recent phenomenon in South America. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Class II HLA interactions modulate genetic risk for multiple sclerosis

PubMed Central

Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

Explorers Program Management

NASA Technical Reports Server (NTRS)

Volpe, Frank; Comberiate, Anthony B. (Technical Monitor)

2001-01-01

The mission of the Explorer Program is to provide frequent flight opportunities for world-class scientific investigations from space within the following space science themes: 1) Astronomical Search for Origins and Planetary Systems; 2) Structure and Evolution of the Universe; and 3) The Sun-Earth Connection. America's space exploration started with Explorer 1 which was launched February 1, 1958 and discovered the Van Allen Radiation Belts. Over 75 Explorer missions have flown. The program seeks to enhance public awareness of, and appreciation for, space science and to incorporate. educational and public outreach activities as integral parts of space science investigations.

Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07.

PubMed

Marino, Fabio; Mommen, Geert P M; Jeko, Anita; Meiring, Hugo D; van Gaans-van den Brink, Jacqueline A M; Scheltema, Richard A; van Els, Cécile A C M; Heck, Albert J R

2017-01-06

Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA peptides have already received attention, arginine methylated HLA class I peptide presentation has not been characterized in detail. In a human B-cell line we detected 149 HLA class I peptides harboring mono- and/or dimethylated arginine residues by mass spectrometry. A striking preference was observed in the presentation of arginine (di)methylated peptides for HLA-B*07 molecules, likely because the binding motifs of this allele resemble consensus sequences recognized by arginine methyl-transferases. Moreover, HLA-B*07-bound peptides preferentially harbored dimethylated groups at the P3 position, thus consecutively to the proline anchor residue. Such a proline-arginine sequence has been associated with the arginine methyl-transferases CARM1 and PRMT5. Making use of the specific neutral losses in fragmentation spectra, we found most of the peptides to be asymmetrically dimethylated, most likely by CARM1. These data expand our knowledge of the processing and presentation of arginine (di)methylated HLA class I peptides and demonstrate that these types of modified peptides can be presented for recognition by T-cells. HLA class I peptides with mono- and dimethylated arginine residues may therefore offer a novel target for immunotherapy.

HLA class I molecules consistently present internal influenza epitopes

PubMed Central

Wahl, Angela; Schafer, Fredda; Bardet, Wilfried; Buchli, Rico; Air, Gillian M.; Hildebrand, William H.

2009-01-01

Cytotoxic T lymphocytes (CTL) limit influenza virus replication and prevent morbidity and mortality upon recognition of HLA class I presented epitopes on the surface of virus infected cells, yet the number and origin of the viral epitopes that decorate the infected cell are unknown. To understand the presentation of influenza virus ligands by human MHC class I molecules, HLA-B*0702-presented viral peptides were directly identified following influenza infection. After transfection with soluble class I molecules, peptide ligands unique to infected cells were eluted from isolated MHC molecules and identified by comparative mass spectrometry (MS). Then CTL were gathered following infection with influenza and viral peptides were tested for immune recognition. We found that the class I molecule B*0702 presents 3–6 viral ligands following infection with different strains of influenza. Peptide ligands derived from the internal viral nucleoprotein (NP418–426 and NP473–481) and from the internal viral polymerase subunit PB1 (PB1329–337) were presented by B*0702 following infection with each of 3 different influenza strains; ligands NP418–426, NP473–481, and PB1329–337 derived from internal viral proteins were consistently revealed by class I HLA. In contrast, ligands derived from hemagglutinin (HA) and matrix protein (M1) were presented intermittently on a strain-by-strain basis. When tested for immune recognition, HLA-B*0702 transgenic mice responded to NP418–426 and PB1329–337 consistently and NP473–481 intermittently while ligands from HA and M1 were not recognized. These data demonstrate an emerging pattern whereby class I HLA reveal a handful of internal viral ligands and whereby CTL recognize consistently presented influenza ligands. PMID:19122146

40 CFR 87.21 - Standards for exhaust emissions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... aircraft gas turbine engine of class T8 manufactured on or after February 1, 1974, shall not exceed: Smoke number of 30. (b) Exhaust emissions of smoke from each new aircraft gas turbine engine of class TF and of... gas turbine engine of class T3 manufactured on or after January 1, 1978, shall not exceed: Smoke...

40 CFR 87.21 - Standards for exhaust emissions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... aircraft gas turbine engine of class T8 manufactured on or after February 1, 1974, shall not exceed: Smoke number of 30. (b) Exhaust emissions of smoke from each new aircraft gas turbine engine of class TF and of... gas turbine engine of class T3 manufactured on or after January 1, 1978, shall not exceed: Smoke...

Characterization of CIA-1, an Ambler class A extended-spectrum β-lactamase from Chryseobacterium indologenes.

PubMed

Matsumoto, Takehisa; Nagata, Mika; Ishimine, Nau; Kawasaki, Kenji; Yamauchi, Kazuyoshi; Hidaka, Eiko; Kasuga, Eriko; Horiuchi, Kazuki; Oana, Kozue; Kawakami, Yoshiyuki; Honda, Takayuki

2012-01-01

An Ambler class A β-lactamase gene, bla(CIA-1), was cloned from the reference strain Chryseobacterium indologenes ATCC 29897 and expressed in Escherichia coli BL21. The bla(CIA-1) gene encodes a novel extended-spectrum β-lactamase (ESBL) that shared 68% and 60% identities with the CGA-1 and CME-1 β-lactamases, respectively. bla(CIA-1)-like genes were detected from clinical isolates. In addition to the metallo-β-lactamase IND of Ambler class B, C. indologenes has a class A ESBL gene, bla(CIA-1), located on the chromosome.

Maltreatment and Mental Health Outcomes among Ultra-Poor Children in Burkina Faso: A Latent Class Analysis

PubMed Central

Ismayilova, Leyla; Gaveras, Eleni; Blum, Austin; Tô-Camier, Alexice; Nanema, Rachel

2016-01-01

Objectives Research about the mental health of children in Francophone West Africa is scarce. This paper examines the relationships between adverse childhood experiences, including exposure to violence and exploitation, and mental health outcomes among children living in ultra-poverty in rural Burkina Faso. Methods This paper utilizes baseline data collected from 360 children ages 10–15 and 360 of their mothers recruited from twelve impoverished villages in the Nord Region of Burkina, located near the Sahel Desert and affected by extreme food insecurity. We used a Latent Class Analysis to identify underlying patterns of maltreatment. Further, the relationships between latent classes and mental health outcomes were tested using mixed effected regression models adjusted for clustering within villages. Results About 15% of the children in the study scored above the clinical cut-off for depression, 17.8% for posttraumatic stress disorder (PTSD), and 6.4% for low self-esteem. The study identified five distinct sub-groups (or classes) of children based on their exposure to adverse childhood experiences. Children with the highest exposure to violence at home, at work and in the community (Abused and Exploited class) and children not attending school and working for other households, often away from their families (External Laborer class), demonstrated highest symptoms of depression and trauma. Despite living in adverse conditions and working to assist families, the study also identified a class of children who were not exposed to any violence at home or at work (Healthy and Non-abused class). Children in this class demonstrated significantly higher self-esteem (b = 0.92, SE = 0.45, p<0.05) and lower symptoms of trauma (b = -3.90, SE = 1.52, p<0.05). Conclusions This study offers insight into the psychological well-being of children in the context of ultra-poverty in Burkina Faso and associated context-specific adverse childhood experiences. Identifying specific sub-groups of children with increased exposure to life stressors has implications for program developers. Study findings indicate a further need to explore the mental health consequences of traumatic experiences within the context of ultra-poverty and to develop integrated economic and psychosocial interventions that prevent or mitigate childhood adversities linked with the family-level poverty and violence in the family. PMID:27764155

Maltreatment and Mental Health Outcomes among Ultra-Poor Children in Burkina Faso: A Latent Class Analysis.

PubMed

Ismayilova, Leyla; Gaveras, Eleni; Blum, Austin; Tô-Camier, Alexice; Nanema, Rachel

2016-01-01

Research about the mental health of children in Francophone West Africa is scarce. This paper examines the relationships between adverse childhood experiences, including exposure to violence and exploitation, and mental health outcomes among children living in ultra-poverty in rural Burkina Faso. This paper utilizes baseline data collected from 360 children ages 10-15 and 360 of their mothers recruited from twelve impoverished villages in the Nord Region of Burkina, located near the Sahel Desert and affected by extreme food insecurity. We used a Latent Class Analysis to identify underlying patterns of maltreatment. Further, the relationships between latent classes and mental health outcomes were tested using mixed effected regression models adjusted for clustering within villages. About 15% of the children in the study scored above the clinical cut-off for depression, 17.8% for posttraumatic stress disorder (PTSD), and 6.4% for low self-esteem. The study identified five distinct sub-groups (or classes) of children based on their exposure to adverse childhood experiences. Children with the highest exposure to violence at home, at work and in the community (Abused and Exploited class) and children not attending school and working for other households, often away from their families (External Laborer class), demonstrated highest symptoms of depression and trauma. Despite living in adverse conditions and working to assist families, the study also identified a class of children who were not exposed to any violence at home or at work (Healthy and Non-abused class). Children in this class demonstrated significantly higher self-esteem (b = 0.92, SE = 0.45, p<0.05) and lower symptoms of trauma (b = -3.90, SE = 1.52, p<0.05). This study offers insight into the psychological well-being of children in the context of ultra-poverty in Burkina Faso and associated context-specific adverse childhood experiences. Identifying specific sub-groups of children with increased exposure to life stressors has implications for program developers. Study findings indicate a further need to explore the mental health consequences of traumatic experiences within the context of ultra-poverty and to develop integrated economic and psychosocial interventions that prevent or mitigate childhood adversities linked with the family-level poverty and violence in the family.

Exploring molecular complexity with ALMA (EMoCA): Detection of three new hot cores in Sagittarius B2(N)

NASA Astrophysics Data System (ADS)

Bonfand, M.; Belloche, A.; Menten, K. M.; Garrod, R. T.; Müller, H. S. P.

2017-08-01

Context. The Sagittarius B2 molecular cloud contains several sites forming high-mass stars. Sgr B2(N) is one of its main centers of activity. It hosts several compact and ultra-compact HII regions, as well as two known hot molecular cores (Sgr B2(N1) and Sgr B2(N2)) in the early stage of the high-mass star formation process, where complex organic molecules (COMs) are detected in the gas phase. Aims: Our goal is to use the high sensitivity of the Atacama Large Millimeter/submillimeter Array (ALMA) to characterize the hot core population in Sgr B2(N) and thereby shed new light on the star formation process in this star-forming region. Methods: We use a complete 3 mm spectral line survey conducted with ALMA to search for faint hot cores in the Sgr B2(N) region. The chemical composition of the detected sources and the column densities are derived by modeling the whole spectra under the assumption of local thermodynamic equilibrium. Population diagrams are constructed to fit rotational temperatures. Integrated intensity maps are produced to derive the peak position and fit the size of each molecule's emission distribution. The kinematic structure of the hot cores is investigated by analyzing the line wing emission of typical outflow tracers. The H2 column densities are computed from ALMA and SMA continuum emission maps. Results: We report the discovery of three new hot cores in Sgr B2(N) that we call Sgr B2(N3), Sgr B2(N4), and Sgr B2(N5). The three sources are associated with class II methanol masers, well known tracers of high-mass star formation, and Sgr B2(N5), also with a UCHII region. Their H2 column densities are found to be between approximately 16 and 36 times lower than the one of the main hot core Sgr B2(N1). The spectra of these new hot cores have spectral line densities of 11 up to 31 emission lines per GHz above the 7σ level, assigned to 22-25 molecules plus 13-20 less abundant isotopologs. We derive rotational temperatures of approximately 140-180 K for the three new hot cores and mean source sizes of 0.4″ for Sgr B2(N3) and 1.0″ for Sgr B2(N4) and Sgr B2(N5). The chemical composition of Sgr B2(N3), Sgr B2(N4), and Sgr B2(N5) is very similar, but it differs from that of Sgr B2(N2). Finally, Sgr B2(N3) and Sgr B2(N5) show high-velocity wing emission in typical outflow tracers, with a bipolar morphology in their integrated intensity maps suggesting the presence of an outflow, like in Sgr B2(N1). No sign of an outflow is found around Sgr B2(N2) and Sgr B2(N4). We derive statistical lifetimes of 4 × 104 yr for the class II methanol maser phase and 6 × 104 yr for the hot core phase in Sgr B2(N). Conclusions: The associations of the hot cores with class II methanol masers, outflows, and/or UCHII regions tentatively suggest the following age sequence: Sgr B2(N4), Sgr B2(N3), SgrB2(N5), Sgr B2(N1). The status of Sgr B2(N2) is unclear. It may contain two distinct sources, a UCHII region and a very young hot core.

Navy Force Structure and Shipbuilding Plans: Background and Issues for Congress

DTIC Science & Technology

2014-08-01

submarines (SSBNs) 12b 12-14b 12b 12b 14 14 14 14 14 Cruise missile submarines (SSGNs) 0c 0-4c 4c 0c 4 4 4 4 2 or 4d Attack submarines ( SSNs ...aircraft carrier 1 1 Virginia ( SSN -774) class attack submarine 2 2 2 2 2 10 Arleigh Burke (DDG-51) class destroyer 2 2 2 2 2 10 Littoral Combat Ship...shows the Navy’s FY2015 30-year (FY2015-FY2044) shipbuilding plan. Table 3. Navy FY2015 30-Year (FY2015-FY2044) Shipbuilding Plan FY CVN LSC SSC SSN

Using Learners' First Language in EFL Classrooms

ERIC Educational Resources Information Center

Alshehri, Eman

2017-01-01

This study explores the attitudes of EFL teachers towards using learners' first language (L1) in their classes. It also considers the frequency and functions of using L1 in EFL classes. A mixed-methods study using questionnaires and follow-up interviews was conducted to collect data from EFL teachers of the preparatory year at a state university…

Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes.

PubMed

Stoney, Patrick N; Helfer, Gisela; Rodrigues, Diana; Morgan, Peter J; McCaffery, Peter

2016-03-01

Thyroid hormone (TH) is essential for adult brain function and its actions include several key roles in the hypothalamus. Although TH controls gene expression via specific TH receptors of the nuclear receptor class, surprisingly few genes have been demonstrated to be directly regulated by TH in the hypothalamus, or the adult brain as a whole. This study explored the rapid induction by TH of retinaldehyde dehydrogenase 1 (Raldh1), encoding a retinoic acid (RA)-synthesizing enzyme, as a gene specifically expressed in hypothalamic tanycytes, cells that mediate a number of actions of TH in the hypothalamus. The resulting increase in RA may then regulate gene expression via the RA receptors, also of the nuclear receptor class. In vivo exposure of the rat to TH led to a significant and rapid increase in hypothalamic Raldh1 within 4 hours. That this may lead to an in vivo increase in RA is suggested by the later induction by TH of the RA-responsive gene Cyp26b1. To explore the actions of RA in the hypothalamus as a potential mediator of TH control of gene regulation, an ex vivo hypothalamic rat slice culture method was developed in which the Raldh1-expressing tanycytes were maintained. These slice cultures confirmed that TH did not act on genes regulating energy balance but could induce Raldh1. RA has the potential to upregulate expression of genes involved in growth and appetite, Ghrh and Agrp. This regulation is acutely sensitive to epigenetic changes, as has been shown for TH action in vivo. These results indicate that sequential triggering of two nuclear receptor signalling systems has the capability to mediate some of the functions of TH in the hypothalamus. © 2015 Wiley Periodicals, Inc.

Molecular Epidemiology of orf513-Bearing Class 1 Integrons in Multiresistant Clinical Isolates from Argentinean Hospitals

PubMed Central

Arduino, Sonia M.; Catalano, Mariana; Orman, Betina E.; Roy, Paul H.; Centrón, Daniela

2003-01-01

The spread of orf513-bearing class 1 integrons is associated with blaCTX-M-2 in gram-negative clinical isolates in Argentina, with In35 being the most frequently found integron (74%). Among 65 isolates without blaCTX-M-2, only one harbored a novel orf513-bearing class 1 integron with the dfrA3b gene. The finding of orf513 not associated with class 1 integrons in two gram-positive strains indicates the widespread occurrence of this putative site-specific recombinase. PMID:14638506

The Role of Questions in the Science Classroom--How Girls and Boys Respond to Teachers' Questions

ERIC Educational Resources Information Center

Eliasson, Nina; Karlsson, Karl Göran; Sørensen, Helene

2017-01-01

The purpose of this study was to explore (a) to what extent male and female science teachers pose different types of questions and (b) if the type of science question posed influences the extent to which boys or girls respond to them. Transcripts of the teacher-student interaction in a whole-class situation were analysed, with attention paid to…

39 CFR 775.5 - Classes of actions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROCEDURES § 775.5 Classes of actions. (a) Actions which normally require an environment impact statement... 40 CFR 1508.27. (b) Actions requiring an environmental assessment. Classes of actions that will require an environmental assessment unless categorically excluded include: (1) Any project that includes...

39 CFR 775.5 - Classes of actions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROCEDURES § 775.5 Classes of actions. (a) Actions which normally require an environment impact statement... 40 CFR 1508.27. (b) Actions requiring an environmental assessment. Classes of actions that will require an environmental assessment unless categorically excluded include: (1) Any project that includes...

39 CFR 775.5 - Classes of actions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROCEDURES § 775.5 Classes of actions. (a) Actions which normally require an environment impact statement... 40 CFR 1508.27. (b) Actions requiring an environmental assessment. Classes of actions that will require an environmental assessment unless categorically excluded include: (1) Any project that includes...

Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors

PubMed Central

Yin, Yanting; de Waal, Parker W.; He, Yuanzheng; Zhao, Li-Hua; Yang, Dehua; Cai, Xiaoqing; Jiang, Yi; Melcher, Karsten; Wang, Ming-Wei; Xu, H. Eric

2017-01-01

The glucagon receptor (GCGR) belongs to the secretin-like (class B) family of G protein-coupled receptors (GPCRs) and is activated by the peptide hormone glucagon. The structures of an activated class B GPCR have remained unsolved, preventing a mechanistic understanding of how these receptors are activated. Using a combination of structural modeling and mutagenesis studies, we present here two modes of ligand-independent activation of GCGR. First, we identified a GCGR-specific hydrophobic lock comprising Met-338 and Phe-345 within the IC3 loop and transmembrane helix 6 (TM6) and found that this lock stabilizes the TM6 helix in the inactive conformation. Disruption of this hydrophobic lock led to constitutive G protein and arrestin signaling. Second, we discovered a polar core comprising conserved residues in TM2, TM3, TM6, and TM7, and mutations that disrupt this polar core led to constitutive GCGR activity. On the basis of these results, we propose a mechanistic model of GCGR activation in which TM6 is held in an inactive conformation by the conserved polar core and the hydrophobic lock. Mutations that disrupt these inhibitory elements allow TM6 to swing outward to adopt an active TM6 conformation similar to that of the canonical β2-adrenergic receptor complexed with G protein and to that of rhodopsin complexed with arrestin. Importantly, mutations in the corresponding polar core of several other members of class B GPCRs, including PTH1R, PAC1R, VIP1R, and CRFR1, also induce constitutive G protein signaling, suggesting that the rearrangement of the polar core is a conserved mechanism for class B GPCR activation. PMID:28356352

Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors.

PubMed

Yin, Yanting; de Waal, Parker W; He, Yuanzheng; Zhao, Li-Hua; Yang, Dehua; Cai, Xiaoqing; Jiang, Yi; Melcher, Karsten; Wang, Ming-Wei; Xu, H Eric

2017-06-16

The glucagon receptor (GCGR) belongs to the secretin-like (class B) family of G protein-coupled receptors (GPCRs) and is activated by the peptide hormone glucagon. The structures of an activated class B GPCR have remained unsolved, preventing a mechanistic understanding of how these receptors are activated. Using a combination of structural modeling and mutagenesis studies, we present here two modes of ligand-independent activation of GCGR. First, we identified a GCGR-specific hydrophobic lock comprising Met-338 and Phe-345 within the IC3 loop and transmembrane helix 6 (TM6) and found that this lock stabilizes the TM6 helix in the inactive conformation. Disruption of this hydrophobic lock led to constitutive G protein and arrestin signaling. Second, we discovered a polar core comprising conserved residues in TM2, TM3, TM6, and TM7, and mutations that disrupt this polar core led to constitutive GCGR activity. On the basis of these results, we propose a mechanistic model of GCGR activation in which TM6 is held in an inactive conformation by the conserved polar core and the hydrophobic lock. Mutations that disrupt these inhibitory elements allow TM6 to swing outward to adopt an active TM6 conformation similar to that of the canonical β 2 -adrenergic receptor complexed with G protein and to that of rhodopsin complexed with arrestin. Importantly, mutations in the corresponding polar core of several other members of class B GPCRs, including PTH1R, PAC1R, VIP1R, and CRFR1, also induce constitutive G protein signaling, suggesting that the rearrangement of the polar core is a conserved mechanism for class B GPCR activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The emission in the region E>0.1MeV during disk and limb faint solar flares

NASA Astrophysics Data System (ADS)

Irene, Arkhangelskaja; Andrew, Arkhangelskiy; Yury, Kotov; Alexandr, Glyanenko; Maria, Kolchina; Alexey, Kirichenko

2013-06-01

Hard X-ray and gamma-ray emission in energy band E>50 keV was first observed by AVS-F apparatus onboard CORONAS-F satellite (detector SONG-D) during some solar flares with classes B and C by GOES classification. Such component registered in flares with duration less than 30 min. However γ-emission up to several tens of MeV was observed during some classes B and C events, which temporal profiles were not corresponded to Neupert effect. For example, during class B2.3 limb solar flare January 7, 2005 maximum observed energy was Emax˜36 MeV and during class B4.6 disk solar event January 12, 2005 maximum observed energy was Emax˜7 MeV. Properties of temporal profiles and energy spectra of faint solar flares, during which emission in the energy band of E>0.1 MeV were registered are discussed in the presented work. There is not any strong correlation between presence or absence of hard X-ray and γ-ray emission and the intensity of soft X-ray emission during solar flares. The one of illustration of this fact is the absence of any observed statistically significant count rate exceed above background level during some class M flares in the energy band E>0.1 MeV. The typical example of such flares is event November 8, 2001 (class M4.2, lasts from 14:59 UT up to 16:00 UT, maximum of soft X-ray emission was at 15:35 UT on GOES data).

Hidden Lineage Complexity of Glycan-Dependent HIV-1 Broadly Neutralizing Antibodies Uncovered by Digital Panning and Native-Like gp140 Trimer.

PubMed

He, Linling; Lin, Xiaohe; de Val, Natalia; Saye-Francisco, Karen L; Mann, Colin J; Augst, Ryan; Morris, Charles D; Azadnia, Parisa; Zhou, Bin; Sok, Devin; Ozorowski, Gabriel; Ward, Andrew B; Burton, Dennis R; Zhu, Jiang

2017-01-01

Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics. In addition to single-chain variable fragments resembling the wild-type bNAbs, digital panning identified variants of PGT124 (a member of the PGT121 class) with a unique insertion in the heavy chain complementarity-determining region 1, as well as intermediates of PGT124 exhibiting notable affinity for the native-like trimer and broad HIV-1 neutralization. In a competition assay, these bNAb intermediates could effectively compete with mouse sera induced by a scaffolded BG505 gp140.681 trimer for the N332 supersite. Our study thus reveals previously unrecognized lineage complexity of the PGT121-class bNAbs and provides an array of library-derived bNAb intermediates for evaluation of immunogens containing the N332 supersite. Digital panning may prove to be a valuable tool in future studies of bNAb diversity and lineage development.

Hidden Lineage Complexity of Glycan-Dependent HIV-1 Broadly Neutralizing Antibodies Uncovered by Digital Panning and Native-Like gp140 Trimer

PubMed Central

He, Linling; Lin, Xiaohe; de Val, Natalia; Saye-Francisco, Karen L.; Mann, Colin J.; Augst, Ryan; Morris, Charles D.; Azadnia, Parisa; Zhou, Bin; Sok, Devin; Ozorowski, Gabriel; Ward, Andrew B.; Burton, Dennis R.; Zhu, Jiang

2017-01-01

Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics. In addition to single-chain variable fragments resembling the wild-type bNAbs, digital panning identified variants of PGT124 (a member of the PGT121 class) with a unique insertion in the heavy chain complementarity-determining region 1, as well as intermediates of PGT124 exhibiting notable affinity for the native-like trimer and broad HIV-1 neutralization. In a competition assay, these bNAb intermediates could effectively compete with mouse sera induced by a scaffolded BG505 gp140.681 trimer for the N332 supersite. Our study thus reveals previously unrecognized lineage complexity of the PGT121-class bNAbs and provides an array of library-derived bNAb intermediates for evaluation of immunogens containing the N332 supersite. Digital panning may prove to be a valuable tool in future studies of bNAb diversity and lineage development. PMID:28883821

Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

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

Malagari, Katerina, E-mail: kmalag@otonet.gr; Pomoni, Mary; Moschouris, Hippocrates, E-mail: hipmosch@gmail.com

Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 {+-} 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 {+-} 2.1 cm. Lesion morphology was one dominant {<=}5 cm (22 %), one dominant >5 cm (41.6 %), multifocal {<=}5more » (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2-64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions {<=}5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.« less

Sperm-binding fibronectin type II-module proteins are genetically linked and functionally related.

PubMed

Ekhlasi-Hundrieser, Mahnaz; Schäfer, Bettina; Philipp, Ute; Kuiper, Heidi; Leeb, Tosso; Mehta, Meenal; Kirchhoff, Christiane; Töpfer-Petersen, Edda

2007-05-01

Fibronectin type II (Fn2) module-containing proteins in the male genital tract are characterized by different numbers of Fn2 modules. Predominantly two classes exist which are distinct by having either two or four Fn2 modules. Minor variants with three Fn2 modules were also found in the human and the porcine epididymis. To reveal their relationship, mRNAs and proteins of representatives of these classes were studied in human, in Sus scrofa, and in rodents. Adult boars expressed members of both classes, i.e. ELSPBP1 and pB1, in subsequent regions of the epididymis, and both were under androgenic control. Human and rodent epididymides, on the other hand, alternatively contained only representatives of one of these two classes, i.e. ELSPBP1 in the human and two different pB1-related counterparts in rodents. ELSPBP1 and pB1-related genomic sequences were closely linked in chromosomal regions HSA 19q and SSC 6 q11-q21; conserved synteny between these regions is well established. On the other hand, in a syntenic region on mouse chromosome 7, ELSPBP1-related sequences were lacking. Tight binding to the sperm membrane via a choline-mediated mechanism was a common feature of the two classes of Fn2-module proteins, suggesting related function(s). However, differences in their regionalized expression patterns along the male genital tract as well as in association sites on the sperm surface suggested a species-specific sequential order in sperm binding.

HLA Class I Alleles Associated with Mortality in Thai Military Recruits with HIV-1 CRF01_AE Infection

PubMed Central

Bosch, Ronald J.; Rangsin, Ram; Chuenchitra, Thippawan; Sirisopana, Narongrid; Kim, Jerome H.; Robb, Merlin L.; Vejbaesya, Sasijit; Paris, Robert M.; Nelson, Kenrad E.

2016-01-01

Abstract In HIV-1-infected patients, variation at the HLA class I locus is associated with disease progression, but few studies have assessed the influence of HLA alleles on HIV-1 CRF01_AE infection, which is dominant in Thailand. We hypothesized that alleles predicted to confer more effective immune responses, such as HLA-B*46, would protect against disease progression. HLA typing was performed on HIV-1 incident cases surviving until 1998–1999 and HIV-1-negative matched controls from Thai army cohorts enrolled between 1991 and 1995. We assessed associations between class I alleles and disease progression subsequent to HLA typing. Ninety-nine HIV-1-incident cases were followed for a median of 3.7 years after HLA typing; during this time, 58 participants died. Two alleles were associated with mortality: HLA B*51 was protective (3-year survival B*51pos vs. B*51neg: 75% vs. 52%; p = 0.034) whereas Cw*04 was deleterious (3-year survival Cw*04pos vs. Cw*04neg: 39% vs. 60%; p = 0.027). HLA-B*46 was not associated with disease progression. Alleles present at different frequencies in HIV-1-incident compared with HIV-1-negative men included HLA-A*02:03, B*35, B*15, and C*08. 1. In conclusion in this Thai army cohort, HLA-B*51 was associated with lower mortality, confirming that this allele, which is protective in clade B HIV-1 infection, has a similar effect on HIV CRF01_AE infection. The deleterious effect of HLA-Cw*04 must be interpreted with caution because it may be in linkage disequilibrium with disease-susceptible HLA-B alleles. We did not find that HLA-B*46 was protective. These findings may inform vaccine development for areas of the world in which HIV-1 CRF01_AE infection is prevalent. PMID:26383907

A DESCRIPTION OF HANKEL OPERATORS OF CLASS \\mathfrak{S}_p FOR p>0, AN INVESTIGATION OF THE RATE OF RATIONAL APPROXIMATION, AND OTHER APPLICATIONS

NASA Astrophysics Data System (ADS)

Peller, V. V.

1985-02-01

The main result is the following description of Hankel operators in the Schatten-von Neumann class \\mathfrak{S}_p when 0: \\displaystyle \\Gamma_\\varphi\\in\\mathfrak{S}_p\\Leftrightarrow \\varphi\\in B_p^{1/p},where \\Gamma_\\varphi is the Hankel operator with symbol \\varphi, and B_p^{1/p} is the Besov class. This result extends results obtained earlier for 1\\leqslant p<+\\infty by the author to the case 0. Also described are the Hankel operators in the Schatten-Lorentz classes \\mathfrak{S}_{pq}, 0, 0. Precise descriptions of classes of functions defined in terms of rational approximation in the bounded mean oscillation norm are given as an application, along with a complete investigation of the case where the decrease is of power order, and some precise results on rational approximation in the L^\\infty-norm. Certain other applications are also considered.Bibliography: 57 titles.

Evidence for idiotypic- and antiidiotypic B-B cellular interaction with the use of cloned antiidiotypic B cell line.

PubMed

Bitoh, S; Fujimoto, S; Yamamoto, H

1990-03-15

Immunization of BALB/c mice with MOPC104E myeloma protein induces antiidiotypic B lymphocytes that have Id-specific enhancing activity on antibody production. The B-B cell interaction was restricted to both Igh and class II MHC. However, anti-Thy-1 and C-treated splenic B cells were maintained for more than 1 y in a mixture of Con A-stimulated splenocyte culture supernatant and synthetic medium. In applying the long term culture method, we have established a cloned B cell line named B19-1d, B19-1d cells are specific to MOPC104E or J558 cross-reactive Id and they express surface mu, lambda but no Ly-1. B19-1d do not spontaneously secrete Ig but produce them upon stimulation with bacterial LPS. The effect of B19-1d cell line on idiotypic antibody production was tested. Addition of only 10 to 100 B19-1d cells into dextran-immune B cell culture greatly enhanced the Id+ antidextran antibody responses. On the contrary, the antidextran antibody production was suppressed by the higher doses of B19-1d cells. The effective cooperation between dextran-immune B cells and B19-1d cloned B cells was restricted to class II MHC. The role of idiotypic- and antiidiotypic B-B cell interaction in immune regulation and repertoire generation was suggested.

Heat Shock Factors HsfB1 and HsfB2b Are Involved in the Regulation of Pdf1.2 Expression and Pathogen Resistance in Arabidopsis

PubMed Central

Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

2009-01-01

In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses. PMID:19529832

Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer

PubMed Central

Zamanian-Daryoush, Maryam; Lindner, Daniel J.; DiDonato, Joseph A.; Wagner, Matthew; Buffa, Jennifer; Rayman, Patricia; Parks, John S.; Westerterp, Marit; Tall, Alan R.; Hazen, Stanley L.

2017-01-01

Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity. In mice with myeloid-specific loss of ABCA1 (Abca1−M/−M; A1−M/−M), tumor growth was inhibited by ∼4.8-fold relative to wild type (WT) animals. Abcg1−M/−M (G1−M/−M) animals were also protected by 2.5-fold relative to WT, with no further inhibition of tumor growth in Abca1/Abcg1 myeloid-specific double knockout animals (DKO). Analyses of tumor-infiltrating immune cells revealed a correlation between tumor protection and decreased presence of the immune suppressive myeloid-derived suppressor cell (MDSC) subsets, Ly-6G+Ly-6CLo and Ly-6GnegLy-6CHi cells. The growth of the syngeneic MB49 murine bladder cancer cells was also inhibited in A1−M/−M mice. Collectively, our studies provide further evidence for an immune modulatory role for cholesterol homeostasis pathways in cancer. PMID:29069761

[Prevalence and determinants of medication during pregnancy by risk class among mothers of liveborn infants].

PubMed

Geib, Lorena Teresinha Consalter; Vargas Filho, Edson Fauth; Geib, Débora; Mesquita, Débora Iasmin; Nunes, Magda Lahorgue

2007-10-01

In order to identify the maternal determinants of the consumption of medication during pregnancy according to risk class, we conducted a population cohort baseline cross-sectional study with 2,262 mothers of liveborn infants in Passo Fundo, Rio Grande do Sul, Brazil. Data were collected from the Information System on Live Births and through home interviews (an instrument adapted from the Maternity Advice Survey). The drugs were classified according to criteria. We conducted bivariate analyses and logistic regression according to the hierarchical model of determination. 80% of the mothers consumed at least one medicine during the pregnancy, distributed in risk classes as follows: A (53.4%), B (18.1%), C (24.46%), D (1.47%), X (0.06%), and V (various) (2.1%). Incomplete prenatal care and maternal age < 20 years determined the consumption of medication in class A and pregnancy complications in classes B, C, and D. In class C, cesarean section and previous abortion also determined consumption, which in class V was independent of the variables analyzed. Maternal factors, especially health complications, determine the consumption of medicines during pregnancy, suggesting that the prescribing physician should orient the safe and proper use of such medication.

Rice ABERRANT PANICLE ORGANIZATION 1, encoding an F-box protein, regulates meristem fate.

PubMed

Ikeda, Kyoko; Ito, Momoyo; Nagasawa, Nobuhiro; Kyozuka, Junko; Nagato, Yasuo

2007-09-01

Inflorescence architecture is one of the most important agronomical traits. Characterization of rice aberrant panicle organization 1 (apo1) mutants revealed that APO1 positively controls spikelet number by suppressing the precocious conversion of inflorescence meristems to spikelet meristems. In addition, APO1 is associated with the regulation of the plastchron, floral organ identity, and floral determinacy. Phenotypic analyses of apo1 and floral homeotic double mutants demonstrate that APO1 positively regulates class-C floral homeotic genes, but not class-B genes. Molecular studies revealed that APO1 encodes an F-box protein, an ortholog of Arabidopsis UNUSUAL FLORAL ORGAN (UFO), which is a positive regulator of class-B genes. Overexpression of APO1 caused an increase in inflorescence branches and spikelets. As the mutant inflorescences and flowers differed considerably between apo1 and ufo, the functions of APO1 and UFO appear to have diverged during evolution.

76 FR 18040 - Amendment of Class E Airspace; West Yellowstone, MT

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

... reference action under 1 CFR Part 51, subject to the annual revision of FAA Order 7400.9 and publication of... CLASS A, B, C, D AND E AIRSPACE AREAS; AIR TRAFFIC SERVICE ROUTES; AND REPORTING POINTS 0 1. The... follows: Paragraph 6005 Class E airspace areas extending upward from 700 feet or more above the surface of...

Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration.

PubMed

Sartori, Luca; Mercurio, Ciro; Amigoni, Federica; Cappa, Anna; Fagá, Giovanni; Fattori, Raimondo; Legnaghi, Elena; Ciossani, Giuseppe; Mattevi, Andrea; Meroni, Giuseppe; Moretti, Loris; Cecatiello, Valentina; Pasqualato, Sebastiano; Romussi, Alessia; Thaler, Florian; Trifiró, Paolo; Villa, Manuela; Vultaggio, Stefania; Botrugno, Oronza A; Dessanti, Paola; Minucci, Saverio; Zagarrí, Elisa; Carettoni, Daniele; Iuzzolino, Lucia; Varasi, Mario; Vianello, Paola

2017-03-09

Lysine specific demethylase 1 KDM1A (LSD1) regulates histone methylation and it is increasingly recognized as a potential therapeutic target in oncology. We report on a high-throughput screening campaign performed on KDM1A/CoREST, using a time-resolved fluorescence resonance energy transfer (TR-FRET) technology, to identify reversible inhibitors. The screening led to 115 hits for which we determined biochemical IC 50 , thus identifying four chemical series. After data analysis, we have prioritized the chemical series of N-phenyl-4H-thieno[3, 2-b]pyrrole-5-carboxamide for which we obtained X-ray structures of the most potent hit (compound 19, IC 50 = 2.9 μM) in complex with the enzyme. Initial expansion of this chemical class, both modifying core structure and decorating benzamide moiety, was directed toward the definition of the moieties responsible for the interaction with the enzyme. Preliminary optimization led to compound 90, which inhibited the enzyme with a submicromolar IC 50 (0.162 μM), capable of inhibiting the target in cells.

Analysis of Features for Synthetic Aperture Radar Target Classification

DTIC Science & Technology

2015-03-26

rewriting the variance of a class after projection as s2c = ∑ n wT (xc,n −mc)(xc,n −mc)T w, = wT Scw, (2.25) where subscript c ∈ [1, 2] is the class...such a case, the distribution of class c is N(mc,SW), where SW is the same as in Equation (2.29). Additionally, if m1 ≈ m2, then w approaches zero as...function of the bandwidth, B, and the speed of light, c , where [8] ρx = c 2B . (2.48) 21 Cross-range resolution, ρy, is a function of the wavelength

Additional information for “TREMOR: A Wireless, MEMS Accelerograph for Dense Arrays” (Evans et al., 2003)

USGS Publications Warehouse

Evans, John R.; Hamstra, Robert H.; Spudich, Paul; Kundig, Christoph; Camina, Patrick; Rogers, John A.

2003-01-01

The length of Evans et al. (2003) necessitated transfer of several less germane sections to this alternate forum to meet that venue’s needs. These sections include a description of the development of Figure 1, the plot of spatial variability so critical to the argument for dense arrays of strong-motion instruments; the description of the rapid, integer, computational method for PGV used in the TREMOR instrument (the Oakland instrument, the commercial prototype, and the commercial instrument); siting methods and strategies used for Class B TREMOR instruments and those that can be used for Class C instruments to preserve the cost advantages of such systems; and some general discussion of MEMS accelerometers, including a comparative Table with representative examples of Class A, B and C MEMS devices. (“MEMS” means “Micro-ElectroMechanical” Systems—“micromachined” sensors, generally of silicon. Classes A, B, and C are defined in Table 1.)

Class I HLA-A*7401 is associated with protection from HIV-1 acquisition and disease progression in Mbeya, Tanzania.

PubMed

Koehler, Rebecca N; Walsh, Anne M; Saathoff, Elmar; Tovanabutra, Sodsai; Arroyo, Miguel A; Currier, Jeffery R; Maboko, Leonard; Hoelscher, Michael; Hoelsher, Michael; Robb, Merlin L; Michael, Nelson L; McCutchan, Francine E; Kim, Jerome H; Kijak, Gustavo H

2010-11-15

Here we explore associations between HLA variation and human immunodeficiency virus type 1 (HIV-1) acquisition and disease progression in a community cohort in Mbeya, Tanzania, a region that, despite harboring high rates of HIV-1 infection, remains understudied. African-specific allele HLA-A*74:01 was associated with decreased risk of infection (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14-0.80; P = .011) and with protection from CD4(+) cell counts <200 cells/uL in women (OR, 0.31; 95% CI, 0.07-0.91; P = .032) and men (OR, 0.15; 95% CI, 0.01-0.78; P = .020). These associations remained significant after adjustment for linkage disequilibrium with HLA-B and HLA-C alleles. This observation calls for additional investigation of mechanisms by which HLA-A*74:01 may influence HIV-1 acquisition and control of the infection.

Kinetics of Sulbactam Hydrolysis by β-Lactamases, and Kinetics of β-Lactamase Inhibition by Sulbactam

PubMed Central

2017-01-01

ABSTRACT Sulbactam is one of four β-lactamase inhibitors in current clinical use to counteract drug resistance caused by degradation of β-lactam antibiotics by these bacterial enzymes. As a β-lactam itself, sulbactam is susceptible to degradation by β-lactamases. I investigated the Michaelis-Menten kinetics of sulbactam hydrolysis by 14 β-lactamases, representing clinically widespread groups within all four Ambler classes, i.e., CTX-M-15, KPC-2, SHV-5, and TEM-1 for class A; IMP-1, NDM-1, and VIM-1 for class B; Acinetobacter baumannii ADC-7, Pseudomonas aeruginosa AmpC, and Enterobacter cloacae P99 for class C; and OXA-10, OXA-23, OXA-24, and OXA-48 for class D. All of the β-lactamases were able to hydrolyze sulbactam, although they varied widely in their kinetic constants for the reaction, even within each class. I also investigated the inactivation kinetics of the inhibition of these enzymes by sulbactam. The class A β-lactamases varied widely in their susceptibility to inhibition, the class C and D enzymes were very weakly inhibited, and the class B enzymes were essentially or completely unaffected. In addition, we measured the sulbactam turnover number, the sulbactam/enzyme molar ratio required for complete inhibition of each enzyme. Class C enzymes had the lowest turnover numbers, class A enzymes varied widely, and class D enzymes had very high turnover numbers. These results are valuable for understanding which β-lactamases ought to be well inhibited by sulbactam. Moreover, since sulbactam has intrinsic antibacterial activity against Acinetobacter species pathogens, these results contribute to understanding β-lactamase-mediated sulbactam resistance in Acinetobacter, especially due to the action of the widespread class D enzymes. PMID:28971872

The HLA dictionary 2008: a summary of HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens.

PubMed

Holdsworth, R; Hurley, C K; Marsh, S G E; Lau, M; Noreen, H J; Kempenich, J H; Setterholm, M; Maiers, M

2009-02-01

The 2008 report of the human leukocyte antigen (HLA) data dictionary presents serologic equivalents of HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, and -DQB1 alleles. The dictionary is an update of the one published in 2004. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for Factors of the HLA System, the International Cell Exchange, UCLA, the National Marrow Donor Program, recent publications, and individual laboratories. The 2008 edition includes information on 832 new alleles (685 class I and 147 class II) and updated information on 766 previously listed alleles (577 class I and 189 class II). The tables list the alleles with remarks on the serologic patterns and the equivalents. The serological equivalents are listed as expert assigned types, and the data are useful for identifying potential stem cell donors who were typed by either serology or DNA-based methods. The tables with HLA equivalents are available as a searchable form on the IMGT/HLA database Web site (http://www.ebi.ac.uk/imgt/hla/dictionary.html).

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass.

PubMed

Engelman, Richard; Baker, Robert A; Likosky, Donald S; Grigore, Alina; Dickinson, Timothy A; Shore-Lesserson, Linda; Hammon, John W

2015-08-01

In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: CLASS I RECOMMENDATIONS: a)The oxygenator arterial outlet blood temperature is recommended to be utilized as a surrogate for cerebral temperature measurement during CPB. (Class I, Level C) b)To monitor cerebral perfusate temperature during warming, it should be assumed that the oxygenator arterial outlet blood temperature under-estimates cerebral perfusate temperature. (Class I, Level C) c)Surgical teams should limit arterial outlet blood temperature to<37°C to avoid cerebral hyperthermia. (Class 1, Level C) d)Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB cooling should not exceed 10°C to avoid generation of gaseous emboli. (Class 1, Level C) e)Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB rewarming should not exceed 10°C to avoid out-gassing when blood is returned to the patient. (Class 1, Level C) CLASS IIa a)Pulmonary artery or nasopharyngeal temperature recording is reasonable for weaning and immediate post-bypass temperature measurement. (Class IIa, Level C)b)Rewarming when arterial blood outlet temperature ≥30° C: i.To achieve the desired temperature for separation from bypass, it is reasonable to maintain a temperature gradient between arterial outlet temperature and the venous inflow of≤4°C. (Class IIa, Level B) ii.To achieve the desired temperature for separation from bypass, it is reasonable to maintain a rewarming rate≤0.5°C/min. (Class IIa, Level B) NO RECOMMENDATION: No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence. Copyright © 2015. Published by Elsevier Inc.

The Class Size Policy Debate. Working Paper No. 121.

ERIC Educational Resources Information Center

Krueger, Alan B.; Hanushek, Eric A.

These papers examine research on the impact of class size on student achievement. After an "Introduction," (Richard Rothstein), Part 1, "Understanding the Magnitude and Effect of Class Size on Student Achievement" (Alan B. Krueger), presents a reanalysis of Hanushek's 1997 literature review, criticizing Hanushek's vote-counting…

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

PubMed Central

Saito, Patricia Keiko; Yamakawa, Roger Haruki; Aparecida, Erica Pereira; da Silva Júnior, Waldir Verissimo; Borelli, Sueli Donizete

2014-01-01

Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples. PMID:24927116

The Cellular Bases of Antibody Responses during Dengue Virus Infection

PubMed Central

Yam-Puc, Juan Carlos; Cedillo-Barrón, Leticia; Aguilar-Medina, Elsa Maribel; Ramos-Payán, Rosalío; Escobar-Gutiérrez, Alejandro; Flores-Romo, Leopoldo

2016-01-01

Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab) responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG) memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell-dependent processes, we know rather little about the (acute, chronic, or memory) B cell responses and the complex cellular mechanisms generating these Abs during DENV infections. This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events such as the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation, and germinal centers (GCs) formation (the source of affinity-matured class-switched memory Abs), till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells, and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated. PMID:27375618

Spatial chaos of Wang tiles with two symbols

NASA Astrophysics Data System (ADS)

Chen, Jin-Yu; Chen, Yu-Jie; Hu, Wen-Guei; Lin, Song-Sun

2016-02-01

This investigation completely classifies the spatial chaos problem in plane edge coloring (Wang tiles) with two symbols. For a set of Wang tiles B , spatial chaos occurs when the spatial entropy h ( B ) is positive. B is called a minimal cycle generator if P ( B ) ≠ 0̸ and P ( B ' ) = 0̸ whenever B ' ⫋ B , where P ( B ) is the set of all periodic patterns on ℤ2 generated by B . Given a set of Wang tiles B , write B = C 1 ∪ C 2 ∪ ⋯ ∪ C k ∪ N , where Cj, 1 ≤ j ≤ k, are minimal cycle generators and B contains no minimal cycle generator except those contained in C1∪C2∪⋯∪Ck. Then, the positivity of spatial entropy h ( B ) is completely determined by C1∪C2∪⋯∪Ck. Furthermore, there are 39 equivalence classes of marginal positive-entropy sets of Wang tiles and 18 equivalence classes of saturated zero-entropy sets of Wang tiles. For a set of Wang tiles B , h ( B ) is positive if and only if B contains a MPE set, and h ( B ) is zero if and only if B is a subset of a SZE set.

Twin Brothers with Autism and Their Intra-Pair Interactions in a Pre-School Special Education Class

ERIC Educational Resources Information Center

Markodimitraki, Maria; Ampartzaki, Maria; Kypriotaki, Maria; Linardakis, Michalis

2017-01-01

The present study focused on the intra-pair interaction of a pair of dizygotic twins with autism in pre-school age and explored: (a) the type of play and the level of symbolic play the twins prefer and are most frequently engaged with; (b) the attitudes the twins usually display; (c) the most frequent initiator of interactions; and (d) the way the…

The Critical Pedagogical Potential of Using Jacob A. Riis' Works about the Immigrant Poor in "Gilded Age" New York

ERIC Educational Resources Information Center

Templer, Bill

2017-01-01

The article seeks to contribute to working-class and social justice pedagogy by developing concrete angles on teaching/exploring some of the (a) short fiction, (b) journalistic-photographic work and (c) sociography of poverty by the Danish-born US immigrant, muckraker (http://goo.gl/6WeGtM) and social reformer Jacob A. Riis (1849-1914,…

Gender inequalities in health: exploring the contribution of living conditions in the intersection of social class

PubMed Central

Malmusi, Davide; Vives, Alejandra; Benach, Joan; Borrell, Carme

2014-01-01

Background Women experience poorer health than men despite their longer life expectancy, due to a higher prevalence of non-fatal chronic illnesses. This paper aims to explore whether the unequal gender distribution of roles and resources can account for inequalities in general self-rated health (SRH) by gender, across social classes, in a Southern European population. Methods Cross-sectional study of residents in Catalonia aged 25–64, using data from the 2006 population living conditions survey (n=5,817). Poisson regression models were used to calculate the fair/poor SRH prevalence ratio (PR) by gender and to estimate the contribution of variables assessing several dimensions of living conditions as the reduction in the PR after their inclusion in the model. Analyses were stratified by social class (non-manual and manual). Results SRH was poorer for women among both non-manual (PR 1.39, 95% CI 1.09–1.76) and manual social classes (PR 1.36, 95% CI 1.20–1.56). Adjustment for individual income alone eliminated the association between sex and SRH, especially among manual classes (PR 1.01, 95% CI 0.85–1.19; among non-manual 1.19, 0.92–1.54). The association was also reduced when adjusting by employment conditions among manual classes, and household material and economic situation, time in household chores and residential environment among non-manual classes. Discussion Gender inequalities in individual income appear to contribute largely to women's poorer health. Individual income may indicate the availability of economic resources, but also the history of access to the labour market and potentially the degree of independence and power within the household. Policies to facilitate women's labour market participation, to close the gender pay gap, or to raise non-contributory pensions may be helpful to improve women's health. PMID:24560257

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

PubMed Central

2011-01-01

Background Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs). Methods Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared. Results Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs. Conclusions A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions. PMID:21362172

26 CFR 1.305-4 - Distributions of common and preferred stock.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the class A stock payable in additional shares of class A stock and a dividend is declared on class B... date of distribution at a price that is only slightly higher than the market price of class A stock on... marketability of the convertible stock, and the conversion price, it is reasonable to anticipate that within a...

49 CFR 1185.1 - Definitions and scope of regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... electric railway not operating as part of the general system of rail transportation), and a corporation... III railroads. 49 U.S.C. 11328(b). (b) When a person is an officer of a Class I railroad and seeks to become an officer of another Class I railroad, an application under 49 U.S.C. 11328(a) (or petition for...

The Class Size Debate.

ERIC Educational Resources Information Center

Mishel, Lawrence, Ed.; Rothstein, Richard, Ed.

This collection of papers debates the merits of smaller class sizes and research methods used to evaluate the efficacy of this education reform measure. Four chapters focus on (1) "Understanding the Magnitude and Effect of Class Size on Student Achievement" (Alan B. Krueger), which discusses expenditures per student and economic criterion; (2)…

22 CFR 40.9 - Classes of inadmissible aliens.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Classes of inadmissible aliens. 40.9 Section 40.9 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND... inadmissible aliens. Subparts B through L describe classes of inadmissible aliens who are ineligible to receive...

22 CFR 40.9 - Classes of inadmissible aliens.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Classes of inadmissible aliens. 40.9 Section 40.9 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND... inadmissible aliens. Subparts B through L describe classes of inadmissible aliens who are ineligible to receive...

22 CFR 40.9 - Classes of inadmissible aliens.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Classes of inadmissible aliens. 40.9 Section 40.9 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND... inadmissible aliens. Subparts B through L describe classes of inadmissible aliens who are ineligible to receive...

22 CFR 40.9 - Classes of inadmissible aliens.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Classes of inadmissible aliens. 40.9 Section 40.9 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND... inadmissible aliens. Subparts B through L describe classes of inadmissible aliens who are ineligible to receive...

22 CFR 40.9 - Classes of inadmissible aliens.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Classes of inadmissible aliens. 40.9 Section 40.9 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND... inadmissible aliens. Subparts B through L describe classes of inadmissible aliens who are ineligible to receive...

78 FR 60745 - Hazardous Materials: Minor Editorial Corrections and Clarifications (RRR)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... 173.62 This section provides packaging instructions for Class 1 explosive materials. Paragraph (b) of... requirements for approval of special form Class 7 (radioactive) materials. Paragraph (d) of this section notes... activity of special form Class 7 (radioactive) material permitted in a Type A package equals the maximum...

37 CFR 201.7 - Cancellation of completed registrations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... registration number is eliminated and a new registration is made under a different class and number. (b...; or (3) An existing registration in the wrong class is to be replaced by a new registration in the correct class. (c) Circumstances under which a registration will be cancelled. (1) Where the Copyright...

Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice Is Critical for Development and Function of Human T and B Cells

PubMed Central

Danner, Rebecca; Chaudhari, Snehal N.; Rosenberger, John; Surls, Jacqueline; Richie, Thomas L.; Brumeanu, Teodor-Doru; Casares, Sofia

2011-01-01

Background Humanized mice able to reconstitute a surrogate human immune system (HIS) can be used for studies on human immunology and may provide a predictive preclinical model for human vaccines prior to clinical trials. However, current humanized mouse models show sub-optimal human T cell reconstitution and limited ability to support immunoglobulin class switching by human B cells. This limitation has been attributed to the lack of expression of Human Leukocyte Antigens (HLA) molecules in mouse lymphoid organs. Recently, humanized mice expressing HLA class I molecules have been generated but showed little improvement in human T cell reconstitution and function of T and B cells. Methods We have generated NOD.Rag1KO.IL2RγcKO mice expressing HLA class II (HLA-DR4) molecules under the I-Ed promoter that were infused as adults with HLA-DR-matched human hematopoietic stem cells (HSC). Littermates lacking expression of HLA-DR4 molecules were used as control. Results HSC-infused HLA-DR4.NOD.Rag1KO.IL-2RγcKO mice developed a very high reconstitution rate (>90%) with long-lived and functional human T and B cells. Unlike previous humanized mouse models reported in the literature and our control mice, the HLA-DR4 expressing mice reconstituted serum levels (natural antibodies) of human IgM, IgG (all four subclasses), IgA, and IgE comparable to humans, and elicited high titers of specific human IgG antibodies upon tetanus toxoid vaccination. Conclusions Our study demonstrates the critical role of HLA class II molecules for development of functional human T cells able to support immunoglobulin class switching and efficiently respond to vaccination. PMID:21611197

Assessment in Performance-Based Secondary Music Classes

ERIC Educational Resources Information Center

Pellegrino, Kristen; Conway, Colleen M.; Russell, Joshua A.

2015-01-01

After sharing research findings about grading and assessment practices in secondary music ensemble classes, we offer examples of commonly used assessment tools (ratings scale, checklist, rubric) for the performance ensemble. Then, we explore the various purposes of assessment in performance-based music courses: (1) to meet state, national, and…

Career Exploration Curriculum Guide. (Prototype).

ERIC Educational Resources Information Center

Great Falls Public Schools, MT.

Materials contained in this curriculum guide include daily lesson plan outlines for an eighteen-week Experience Based Career Education (EBCE) class. Learning experiences are suggested to meet the following major objectives of the class: (1) Develop students' understanding of the role of work in society and the multiple aspects of their career…

Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

PubMed

Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

2018-02-01

Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

Interferon Gamma-1b Injection

MedlinePlus

... in people with severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of ... you may have flu-like symptoms such as headache, fever, chills, muscle aches, and tiredness after your ...

78 FR 76781 - Proposed Modification of Class B Airspace; Salt Lake City, UT

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... City, UT AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking... City Class B airspace area by raising the floor of a small portion of Class B airspace between the Salt Lake City Class B surface area and the Hill Air Force Base (AFB) Class D airspace area. This action...

A Triad of Molecular Regions Contribute to the Formation of Two Distinct MHC Class II Conformers

PubMed Central

Drake, Lisa A.; Drake, James R.

2016-01-01

MHC class II molecules present antigen-derived peptides to CD4 T cells to drive the adaptive immune response. Previous work has established that class II αβ dimers can adopt two distinct conformations, driven by the differential pairing of transmembrane domain GxxxG dimerization motifs. These class II conformers differ in their ability to be loaded with antigen-derived peptide and to effectively engage CD4 T cells. Motif 1 (M1) paired I-Ak class II molecules are efficiently loaded with peptides derived from the processing of B cell receptor-bound antigen, have unique B cell signaling properties and high T cell stimulation activity. The 11-5.2 mAb selectively binds M1 paired I-Ak class II molecules. However, the molecular determinants of 11-5.2 binding are currently unclear. Here, we report the ability of a human class II transmembrane domain to drive both M1 and M2 class II conformer formation. Protease sensitivity analysis further strengthens the idea that there are conformational differences between the extracellular domains of M1 and M2 paired class II. Finally, MHC class II chain alignments and site directed mutagenesis reveals a triad of molecular regions that contributes to 11-5.2 mAb binding. In addition to transmembrane GxxxG motif domain pairing, 11-5.2 binding is influenced directly by α chain residue Glu-71 and indirectly by the region around the inter-chain salt bridge formed by α chain Arg-52 and β chain Glu-86. These findings provide insight into the complexity of 11-5.2 mAb recognition of the M1 paired I-Ak class II conformer and further highlight the molecular heterogeneity of peptide-MHC class II complexes that drive T cell antigen recognition. PMID:27148821

Genetic and epigenetic alteration among three homoeologous genes of a class E MADS box gene in hexaploid wheat.

PubMed

Shitsukawa, Naoki; Tahira, Chikako; Kassai, Ken-Ichiro; Hirabayashi, Chizuru; Shimizu, Tomoaki; Takumi, Shigeo; Mochida, Keiichi; Kawaura, Kanako; Ogihara, Yasunari; Murai, Koji

2007-06-01

Bread wheat (Triticum aestivum) is a hexaploid species with A, B, and D ancestral genomes. Most bread wheat genes are present in the genome as triplicated homoeologous genes (homoeologs) derived from the ancestral species. Here, we report that both genetic and epigenetic alterations have occurred in the homoeologs of a wheat class E MADS box gene. Two class E genes are identified in wheat, wheat SEPALLATA (WSEP) and wheat LEAFY HULL STERILE1 (WLHS1), which are homologs of Os MADS45 and Os MADS1 in rice (Oryza sativa), respectively. The three wheat homoeologs of WSEP showed similar genomic structures and expression profiles. By contrast, the three homoeologs of WLHS1 showed genetic and epigenetic alterations. The A genome WLHS1 homoeolog (WLHS1-A) had a structural alteration that contained a large novel sequence in place of the K domain sequence. A yeast two-hybrid analysis and a transgenic experiment indicated that the WLHS1-A protein had no apparent function. The B and D genome homoeologs, WLHS1-B and WLHS1-D, respectively, had an intact MADS box gene structure, but WLHS1-B was predominantly silenced by cytosine methylation. Consequently, of the three WLHS1 homoeologs, only WLHS1-D functions in hexaploid wheat. This is a situation where three homoeologs are differentially regulated by genetic and epigenetic mechanisms.

Automatic Identification Systems the Effects of Class B on the Use of Class A Systems

NASA Astrophysics Data System (ADS)

Norris, Andy

2006-05-01

The standards for CSTDMA Class B AIS will shortly be published by the International Electrotechnical Commission and equipment will become available during 2006. The perceived benefits that Class B brings to leisure craft users and its relatively low cost will make it attractive in the market place. A rapid take-up of Class B use can therefore be expected. This paper considers the impact that increased use of Class B will have on users of Class A AIS that are compulsorily fitted to larger vessels to meet the requirements of the International Maritime Organization Safety of Life at Sea convention. The CSTDMA Class B system has been designed to prevent overloading of the AIS VHF data link. This is briefly reviewed but there are a number of other aspects that need to be considered. These include: the increased garbling of Class B messages compared to those of Class A; the problems accruing from the low update rate of Class B information; the increase in display information that will need to be managed; and the possible increase in inappropriate manoeuvres of leisure craft caused by misplaced reliance on AIS. As a result of the investigation the paper highlights the fact that Class B users must not assume that their own presence, in the form of Class B transmissions, will be particularly visible on the bridge of many SOLAS vessels. This will continue to be the case for many years into the future, until such vessels are mandated to carry radar with AIS target overlay capability.

Polymorphic Homoeolog of Key Gene of RdDM Pathway, ARGONAUTE4_9 class Is Associated with Pre-Harvest Sprouting in Wheat (Triticum aestivum L.)

PubMed Central

Singh, Manjit; Singh, Surinder; Randhawa, Harpinder; Singh, Jaswinder

2013-01-01

Resistance to pre-harvest sprouting (PHS) is an important objective for the genetic improvement of many cereal crops, including wheat. Resistance, or susceptibility, to PHS is mainly influenced by seed dormancy, a complex trait. Reduced seed dormancy is the most important aspect of seed germination on a spike prior to harvesting, but it is influenced by various environmental factors including light, temperature and abiotic stresses. The basic genetic framework of seed dormancy depends on the antagonistic action of abscisic acid (ABA) and gibberellic acid (GA) to promote dormancy and germination. Recent studies have revealed a role for epigenetic changes, predominantly histone modifications, in controlling seed dormancy. To investigate the role of DNA methylation in seed dormancy, we explored the role of ARGONAUTE4_9 class genes in seed development and dormancy in wheat. Our results indicate that the two wheat AGO4_9 class genes i.e. AGO802 and AGO804 map to chromosomes 3S and 1S are preferentially expressed in the embryos of developing seeds. Differential expressions of AGO802-B in the embryos of PHS resistant and susceptible varieties also relates with DNA polymorphism in various wheat varieties due to an insertion of a SINE-like element into this gene. DNA methylation patterns of the embryonic tissue from six PHS resistant and susceptible varieties demonstrate a correlation with this polymorphism. These results suggest a possible role for AGO802-B in seed dormancy and PHS resistance through the modulation of DNA methylation. PMID:24130825

Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response

PubMed Central

Halperin, John J.; Kurlan, Roger; Schwalb, Jason M.; Cusimano, Michael D.; Gronseth, Gary; Gloss, David

2015-01-01

Objective: We evaluated evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness. Methods: We identified and classified relevant published studies according to 2004 and 2011 American Academy of Neurology methodology. Results: Of 21 articles, we identified 3 Class I articles. Conclusions: Shunting is possibly effective in iNPH (96% chance subjective improvement, 83% chance improvement on timed walk test at 6 months) (3 Class III). Serious adverse event risk was 11% (1 Class III). Predictors of success included elevated Ro (1 Class I, multiple Class II), impaired cerebral blood flow reactivity to acetazolamide (by SPECT) (1 Class I), and positive response to either external lumbar drainage (1 Class III) or repeated lumbar punctures. Age may not be a prognostic factor (1 Class II). Data are insufficient to judge efficacy of radionuclide cisternography or aqueductal flow measurement by MRI. Recommendations: Clinicians may choose to offer shunting for subjective iNPH symptoms and gait (Level C). Because of significant adverse event risk, risks and benefits should be carefully weighed (Level B). Clinicians should inform patients with iNPH with elevated Ro and their families that they have an increased chance of responding to shunting compared with those without such elevation (Level B). Clinicians may counsel patients with iNPH and their families that (1) positive response to external lumbar drainage or to repeated lumbar punctures increases the chance of response to shunting, and (2) increasing age does not decrease the chance of shunting being successful (both Level C). PMID:26644048

Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function

PubMed Central

Vasquez, Marcos; Fioravanti, Jessica; Aranda, Fernando; Paredes, Vladimir; Gomar, Celia; Ardaiz, Nuria; Fernandez-Ruiz, Veronica; Méndez, Miriam; Nistal-Villan, Estanislao; Larrea, Esther; Gao, Qinshan; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Berraondo, Pedro

2016-01-01

ABSTRACT Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFNα co-expressing in the liver a SR-B1 ligand and IFNα by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFNα signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFNα enhancers while SR-B1 inhibitors dampen IFNα activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFNα and oncolytic viruses. PMID:27622065

Children's Responses to Mother-Infant and Father-Infant Interaction with a Baby Sibling: Jealousy or Joy?

PubMed Central

Volling, Brenda L.; Yu, Tianyi; Gonzalez, Richard; Kennedy, Denise E.; Rosenberg, Lauren; Oh, Wonjung

2014-01-01

Firstborn children's reactions to mother-infant and father-infant interaction after a sibling's birth were examined in an investigation of 224 families. Triadic observations of parent-infant-sibling interaction were conducted at 1 month after the birth. Parents reported on children's problem behaviors at 1 and 4 months after the birth, and completed the Attachment Q-sort before the birth. Latent Profile Analysis (LPA) identified four latent classes (behavioral profiles) for mother-infant and father-infant interaction: regulated-exploration, disruptive-dysregulated, approach-avoidant, and anxious-clingy. A fifth class, attention-seeking, was found with fathers. The regulated-exploration class was the normative pattern (60%), with few children in the disruptive class (2.7%). Approach-avoidant children had more behavior problems at 4 months than any other class with the exception of the disruptive children who were higher on aggression and attention problems. Before the birth, anxious-clingy children had less secure attachments to their fathers than approach avoidant children, but more secure attachments to their mothers. Results underscore individual differences in firstborns' behavioral responses to parent-infant interaction and the importance of a person-centered approach for understanding children's jealousy. PMID:25150371

Constructing Class: Exploring the Lived Experience of White Female Student Affairs Professionals from Working Class Families

ERIC Educational Resources Information Center

Svoboda, Victoria

2012-01-01

Researchers have explored the issue of social class in higher education through the experiences of students and faculty, but have not yet analyzed the experiences of student affairs staff. Past researchers have conflated or ignored issues of race in studies on class, and rarely acknowledge gender as a variable in the classed experience. Student…

Signature Patterns of MHC Diversity in Three Gombe Communities of Wild Chimpanzees Reflect Fitness in Reproduction and Immune Defense against SIVcpz.

PubMed

Wroblewski, Emily E; Norman, Paul J; Guethlein, Lisbeth A; Rudicell, Rebecca S; Ramirez, Miguel A; Li, Yingying; Hahn, Beatrice H; Pusey, Anne E; Parham, Peter

2015-05-01

Major histocompatibility complex (MHC) class I molecules determine immune responses to viral infections. These polymorphic cell-surface glycoproteins bind peptide antigens, forming ligands for cytotoxic T and natural killer cell receptors. Under pressure from rapidly evolving viruses, hominoid MHC class I molecules also evolve rapidly, becoming diverse and species-specific. Little is known of the impact of infectious disease epidemics on MHC class I variant distributions in human populations, a context in which the chimpanzee is the superior animal model. Population dynamics of the chimpanzees inhabiting Gombe National Park, Tanzania have been studied for over 50 years. This population is infected with SIVcpz, the precursor of human HIV-1. Because HLA-B is the most polymorphic human MHC class I molecule and correlates strongly with HIV-1 progression, we determined sequences for its ortholog, Patr-B, in 125 Gombe chimpanzees. Eleven Patr-B variants were defined, as were their frequencies in Gombe's three communities, changes in frequency with time, and effect of SIVcpz infection. The growing populations of the northern and central communities, where SIVcpz is less prevalent, have stable distributions comprising a majority of low-frequency Patr-B variants and a few high-frequency variants. Driving the latter to high frequency has been the fecundity of immigrants to the northern community, whereas in the central community, it has been the fecundity of socially dominant individuals. In the declining population of the southern community, where greater SIVcpz prevalence is associated with mortality and emigration, Patr-B variant distributions have been changing. Enriched in this community are Patr-B variants that engage with natural killer cell receptors. Elevated among SIVcpz-infected chimpanzees, the Patr-B*06:03 variant has striking structural and functional similarities to HLA-B*57, the human allotype most strongly associated with delayed HIV-1 progression. Like HLA-B*57, Patr-B*06:03 correlates with reduced viral load, as assessed by detection of SIVcpz RNA in feces.

Feasibility Report and Preliminary Design Proposal Transport and Loading of New Class A, Mk 21/36, New Class B and Class C Weapons into Strike and Transport Aircraft

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

Division 1284

1956-12-01

The primary purpose of this report was to discuss the feasibility of developing a trailer which would pick-up, transport, position, & load the Class A bomb into the B-52 aircraft and the Mk 21/38 or Class B & C bombs into a B-47, B-52, C-124, or C-133.

Ebselen and analogs as inhibitors of Bacillus anthracis thioredoxin reductase and bactericidal antibacterials targeting Bacillus species, Staphylococcus aureus and Mycobacterium tuberculosis.

PubMed

Gustafsson, Tomas N; Osman, Harer; Werngren, Jim; Hoffner, Sven; Engman, Lars; Holmgren, Arne

2016-06-01

Bacillus anthracis is the causative agent of anthrax, a disease associated with a very high mortality rate in its invasive forms. We studied a number of ebselen analogs as inhibitors of B. anthracis thioredoxin reductase and their antibacterial activity on Bacillus subtilis, Staphylococcus aureus, Bacillus cereus and Mycobacterium tuberculosis. The most potent compounds in the series gave IC(50) values down to 70 nM for the pure enzyme and minimal inhibitory concentrations (MICs) down to 0.4 μM (0.12 μg/ml) for B. subtilis, 1.5 μM (0.64 μg/ml) for S. aureus, 2 μM (0.86 μg/ml) for B. cereus and 10 μg/ml for M. tuberculosis. Minimal bactericidal concentrations (MBCs) were found at 1-1.5 times the MIC, indicating a general, class-dependent, bactericidal mode of action. The combined bacteriological and enzymological data were used to construct a preliminary structure-activity-relationship for the benzoisoselenazol class of compounds. When S. aureus and B. subtilis were exposed to ebselen, we were unable to isolate resistant mutants on both solid and in liquid medium suggesting a high resistance barrier. These results suggest that ebselen and analogs thereof could be developed into a novel antibiotic class, useful for the treatment of infections caused by B. anthracis, S. aureus, M. tuberculosis and other clinically important bacteria. Furthermore, the high barrier against resistance development is encouraging for further drug development. We have characterized the thioredoxin system from B. anthracis as a novel drug target and ebselen and analogs thereof as a potential new class of antibiotics targeting several important human pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Single-Use Sensor Strips for Reliable Field Analysis of Gunshot Residue

DTIC Science & Technology

2013-10-13

3    List of Figures Fig. 1. Cyclic square-wave voltammogram at the bare GCE for a mixture of trace metals and explosives constituents of GSR: 3...variables obtained after CVA analysis of the GSR samples according to (B) exposure level or (C) 3-class response mode. Samples in (B) correspond to...to (A) exposure level or (B) 3-class response mode. Samples correspond to the same controls outlined in Fig. 6. Fig. 8. Score plot of the

Crystallization and preliminary crystallographic analysis of the catechol 2,3-dioxygenase PheB from Bacillus stearothermophilus BR219

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

Sugimoto, Keisuke; Matsufuzi, Kazuki; Ohnuma, Hiroaki

2006-02-01

PheB, an extradiol-cleaving catecholic dioxygenase, was crystallized by the hanging-drop vapour-diffusion method using PEG 4000 as a precipitant. The crystal belongs to the orthorhombic system, space group P2{sub 1}2{sub 1}2{sub 1}, and diffracts to 2.3 Å resolution. Class II extradiol-cleaving catecholic dioxygenase, a key enzyme of aromatic compound degradation in bacteria, cleaves the aromatic ring of catechol by adding two O atoms. PheB is one of the class II extradiol-cleaving catecholic dioxygenases and shows a high substrate specificity for catechol derivatives, which have one aromatic ring. In order to reveal the mechanism of the substrate specificity of PheB, PheB hasmore » been crystallized by the hanging-drop vapour-diffusion method using PEG 4000 as a precipitant. The space group of the obtained crystal was P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 65.5, b = 119.2, c = 158.7 Å. The crystal diffracted to 2.3 Å resolution.« less

26 CFR 1.45G-1 - Railroad track maintenance credit.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and J incurred QRTME in the amount of $1 million. Also, on December 6, 2006, J assigned for purposes... (b)(6) of this section) of a Class II railroad or Class III railroad during the taxable year, but... railroad track maintenance credit for the taxable year—(1) General amount. Except as provided in paragraph...

26 CFR 1.45G-1 - Railroad track maintenance credit.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and J incurred QRTME in the amount of $1 million. Also, on December 6, 2006, J assigned for purposes... (b)(6) of this section) of a Class II railroad or Class III railroad during the taxable year, but... railroad track maintenance credit for the taxable year—(1) General amount. Except as provided in paragraph...

26 CFR 1.45G-1 - Railroad track maintenance credit.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and J incurred QRTME in the amount of $1 million. Also, on December 6, 2006, J assigned for purposes... (b)(6) of this section) of a Class II railroad or Class III railroad during the taxable year, but... railroad track maintenance credit for the taxable year—(1) General amount. Except as provided in paragraph...

26 CFR 1.45G-1 - Railroad track maintenance credit.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and J incurred QRTME in the amount of $1 million. Also, on December 6, 2006, J assigned for purposes... (b)(6) of this section) of a Class II railroad or Class III railroad during the taxable year, but... railroad track maintenance credit for the taxable year—(1) General amount. Except as provided in paragraph...

Thermal characteristics of multi-wavelength emission during a B8.3 flare occurred on July 04, 2009

NASA Astrophysics Data System (ADS)

Awasthi, Arun Kumar; Sylwester, Barbara; Sylwester, Janusz; Jain, Rajmal

2015-08-01

We explore the temporal evolution of flare plasma parameters including temperature (T) - differential emission measure (DEM) relationship by analyzing high spectral and temporal cadence X-ray emission in 1.2-20 keV energy band, recorded by SphinX (Polish) and Solar X-ray Spectrometer (SOXS; Indian) instruments, during a B8.3 flare which occurred on July 04, 2009. SphinX records X-ray emission in 1.2-15 keV energy band with the temporal and spectral cadence as good as 6µs and 0.4 keV, respectively. On the other hand, SOXS provides X-ray observations in 4-25 keV energy band with the temporal and spectral resolution of 3s and 0.7 keV, respectively. In addition, we integrate co-temporal EUV line emission in 171, 194 and 284 angstrom obtained from STEREO mission in order to explore low-temperature response to the flare emission. In order to fit observed evolution of multi-wavelength emission during the flare, we incorporate multi-Gaussian and well-established Withbroe - Sylwester maximum likelihood DEM inversion algorithms. Thermal energetics are also estimated using geometrically corrected flaring loop structure obtained through EUV images of the active region from STEREO twin satellites. In addition, we also study the trigger and energy release scenario of this low-intensity class flare in terms of magnetic field as well as multi-wavelength emission.

Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization.

PubMed

Castañeda, Alejandro R; Pinkerton, Kent E; Bein, Keith J; Magaña-Méndez, Alfonso; Yang, Houa T; Ashwood, Paul; Vogel, Christoph F A

2018-08-01

The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL/6 wildtype or AhR knockout (AhR -/- ) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR -/- BMDCs with autologous naive T cells. PM 2.5 significantly induced AhR DNA binding activity to dioxin responsive elements (DRE) and expression of the AhR repressor (AhRR), cytochrome P450 (CYP) 1A1, and CYP1B1, indicating activation of the AhR. In activated (OVA sensitized) BMDCs, PM 2.5 induced interleukin (IL)-1β, CD80, CD86, and MHC class II, suggesting enhanced DC activation, co-stimulation, and antigen presentation; responses that were abolished in AhR deficient DCs. DC-T cell co-cultures treated with PM and lipopolysaccharide (LPS) led to elevated IL-17A and IL-22 expression at the mRNA level, which is mediated by the AhR. PM-treated DCs were essential in endowing T cells with a Th17-phenotype, which was associated with enhanced expression of MHC class II and cyclooxygenase (COX)-2. In conclusion, PM enhances DC activation that primes naive T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen

DOE PAGES

Jardine, Joseph G.; Kulp, Daniel W.; Havenar-Daughton, Colin; ...

2016-03-25

Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. We employed deep mutational scanning and multi-target optimization to develop a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen asmore » a candidate human vaccine prime. Lastly, these methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.« less

HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen

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

Jardine, Joseph G.; Kulp, Daniel W.; Havenar-Daughton, Colin

Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. We employed deep mutational scanning and multi-target optimization to develop a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen asmore » a candidate human vaccine prime. Lastly, these methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.« less

HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.

PubMed

Jardine, Joseph G; Kulp, Daniel W; Havenar-Daughton, Colin; Sarkar, Anita; Briney, Bryan; Sok, Devin; Sesterhenn, Fabian; Ereño-Orbea, June; Kalyuzhniy, Oleksandr; Deresa, Isaiah; Hu, Xiaozhen; Spencer, Skye; Jones, Meaghan; Georgeson, Erik; Adachi, Yumiko; Kubitz, Michael; deCamp, Allan C; Julien, Jean-Philippe; Wilson, Ian A; Burton, Dennis R; Crotty, Shane; Schief, William R

2016-03-25

Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens. Copyright © 2016, American Association for the Advancement of Science.

NASA's Space Launch System: SmallSat Deployment to Deep Space

NASA Technical Reports Server (NTRS)

Robinson, Kimberly F.; Creech, Stephen D.

2017-01-01

Leveraging the significant capability it offers for human exploration and flagship science missions, NASA's Space Launch System (SLS) also provides a unique opportunity for lower-cost deep-space science in the form of small-satellite secondary payloads. Current plans call for such opportunities to begin with the rocket's first flight; a launch of the vehicle's Block 1 configuration, capable of delivering 70 metric tons (t) to Low Earth Orbit (LEO), which will send the Orion crew vehicle around the moon and return it to Earth. On that flight, SLS will also deploy 13 CubeSat-class payloads to deep-space destinations. These secondary payloads will include not only NASA research, but also spacecraft from industry and international partners and academia. The payloads also represent a variety of disciplines including, but not limited to, studies of the moon, Earth, sun, and asteroids. While the SLS Program is making significant progress toward that first launch, preparations are already under way for the second, which will see the booster evolve to its more-capable Block 1B configuration, able to deliver 105t to LEO. That configuration will have the capability to carry large payloads co-manifested with the Orion spacecraft, or to utilize an 8.4-meter (m) fairing to carry payloads several times larger than are currently possible. The Block 1B vehicle will be the workhorse of the Proving Ground phase of NASA's deep-space exploration plans, developing and testing the systems and capabilities necessary for human missions into deep space and ultimately to Mars. Ultimately, the vehicle will evolve to its full Block 2 configuration, with a LEO capability of 130 metric tons. Both the Block 1B and Block 2 versions of the vehicle will be able to carry larger secondary payloads than the Block 1 configuration, creating even more opportunities for affordable scientific exploration of deep space. This paper will outline the progress being made toward flying smallsats on the first flight of SLS, and discuss future opportunities for smallsats on subsequent flights.

49 CFR 176.118 - Electrical requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Electrical requirement. 176.118 Section 176.118... Requirements for Class 1 (Explosive) Materials Stowage § 176.118 Electrical requirement. (a) Electrical... person. (b) Electrical equipment and cables in a cargo space in which Class 1 (explosive) materials are...

49 CFR 176.118 - Electrical requirement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Electrical requirement. 176.118 Section 176.118... Requirements for Class 1 (Explosive) Materials Stowage § 176.118 Electrical requirement. (a) Electrical... person. (b) Electrical equipment and cables in a cargo space in which Class 1 (explosive) materials are...

49 CFR 176.118 - Electrical requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Electrical requirement. 176.118 Section 176.118... Requirements for Class 1 (Explosive) Materials Stowage § 176.118 Electrical requirement. (a) Electrical... person. (b) Electrical equipment and cables in a cargo space in which Class 1 (explosive) materials are...

49 CFR 176.118 - Electrical requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Electrical requirement. 176.118 Section 176.118... Requirements for Class 1 (Explosive) Materials Stowage § 176.118 Electrical requirement. (a) Electrical... person. (b) Electrical equipment and cables in a cargo space in which Class 1 (explosive) materials are...

49 CFR 176.118 - Electrical requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Electrical requirement. 176.118 Section 176.118... Requirements for Class 1 (Explosive) Materials Stowage § 176.118 Electrical requirement. (a) Electrical... person. (b) Electrical equipment and cables in a cargo space in which Class 1 (explosive) materials are...

Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal 
Structures

PubMed Central

Doré, Andrew S.; Bortolato, Andrea; Hollenstein, Kaspar; Cheng, Robert K.Y.; Read, Randy J.; Marshall, Fiona H.

2017-01-01

The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Cor-ticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the trans-membrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hex-agonal setting with translational non-crystallographic symmetry. Molecular dynamics and metadynamics simulations on this novel structure and the existing TMD structure for CRF1R provides insight as to how the small molecule ligand gains access to the induced-fit allosteric binding site with implications for the observed selectivity against CRF2R. Furthermore, molecular dynamics simulations performed using a full-length receptor model point to key interactions between the ECD and extracellular loop 3 of the TMD providing insight into the full inactive state of multidomain class B GPCRs. PMID:28183242

Analysis of Staphylococcal cassette chromosome mec in Staphylococcus haemolyticus and Staphylococcus sciuri: identification of a novel ccr gene complex with a newly identified ccrA allotype (ccrA7).

PubMed

Urushibara, Noriko; Paul, Shyamal Kumar; Hossain, Mohammad Akram; Kawaguchiya, Mitsuyo; Kobayashi, Nobumichi

2011-06-01

Methicillin resistance in staphylococci is conferred by the acquisition in its chromosome of the mecA gene, which is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). Genetic type of SCCmec is defined by combination of mec gene complex class and cassette chromosome recombinase gene (ccr) allotype. In this study, we analyzed genetic diversity of the SCCmec in 11 Staphylococcus haemolyticus strains and a Staphylococcus sciuri strain, which were recently isolated from clinical specimens in Bangladesh. Among these strains, only two S. haemolyticus strains were proved to have the known types of SCCmec, that is, SCCmec V (class C2 mec-ccrC) and VII (class C1 mec-ccrC). Five S. haemolyticus strains were assigned two unique mec-ccr gene complexes combination; that is, class C1 mec-ccrA4B4 (four isolates) and class A mec-ccrC (one isolate). In the remaining four S. haemolyticus strains with class C1 mec, no known ccr allotypes could be detected. A single S. sciuri strain with class A mec complex carried a ccrA gene belonging to a novel allotype designated ccrA7, together with ccrB3. The ccrA7 gene in the S. sciuri strain showed 61.7%-82.7% sequence identity to the ccrA gene sequences published so far, and 75.3% identity to ccrA3, which is a component of the type 3 ccr complex (ccrA3-ccrB3) in methicillin-resistant Staphylococcus aureus. The results of the present study indicated that mec gene complex and ccr genes in coagulase-negative staphylococci are highly divergent, and distinct from those of common methicillin-resistant S. aureus. Identification of the novel ccrA7 allotype combined with ccrB3 suggested an occurrence of recombination between different ccr complexes in nature.

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft by Tim Wright of Jacobs Technology. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidate Christina Hammock listens to a briefing on preparations for the launch the Orion spacecraft on Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on preparations for the launch the Orion spacecraft on Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.

PubMed

Zhao, Li-Hua; Yin, Yanting; Yang, Dehua; Liu, Bo; Hou, Li; Wang, Xiaoxi; Pal, Kuntal; Jiang, Yi; Feng, Yang; Cai, Xiaoqing; Dai, Antao; Liu, Mingyao; Wang, Ming-Wei; Melcher, Karsten; Xu, H Eric

2016-07-15

G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase.

PubMed

Bago, Ruzica; Malik, Nazma; Munson, Michael J; Prescott, Alan R; Davies, Paul; Sommer, Eeva; Shpiro, Natalia; Ward, Richard; Cross, Darren; Ganley, Ian G; Alessi, Dario R

2014-11-01

The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50 in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4-phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K.

Stress, cortisol, and B lymphocytes: a novel approach to understanding academic stress and immune function.

PubMed

McGregor, Bonnie A; Murphy, Karly M; Albano, Denise L; Ceballos, Rachel M

2016-01-01

Animal and human in vitro models suggest that stress-related B lymphocyte decrements are due to high levels of glucocorticoids which cause apoptosis of pre-B-cells as they emerge from the bone marrow. The present study sought to explore the relationships among distress, salivary cortisol, and human B lymphocytes in vivo. Distress (perceived stress, negative affect, depressive symptoms), lymphocyte phenotype, and salivary cortisol were assessed among first-year graduate students (n = 22) and a community control sample (n = 30) at the start of classes in the fall and the week immediately before spring preliminary exams. Compared to controls, students reported greater distress on all measures at each time point except baseline perceived stress. Hierarchical linear regression with necessary control variables was used to assess the effect of student status on the three measures of distress, the four measures of lymphocyte phenotype, and cortisol AUC and CAR over time (T1-T2). Student status was associated with a significant decrease in CD19 + B lymphocytes and flattened cortisol awakening response (CAR). Change in CAR was associated with the decrease in CD19 + B lymphocytes. Results indicated that there are significant associations among student status, flattening of CAR, and decrements in CD19 + lymphocytes.

Major histocompatibility complex class I-deficient NOD-B2mnull mice are diabetes and insulitis resistant.

PubMed

Serreze, D V; Leiter, E H; Christianson, G J; Greiner, D; Roopenian, D C

1994-03-01

Specific allelic combinations within the class II region of the major histocompatibility complex (MHC) represent a major genetic component for susceptibility to autoimmune insulin-dependent diabetes mellitus (IDDM) in humans. We produced and used a stock of NOD/Lt mice congenic for a functionally inactivated beta 2-microglobulin (B2mnull) locus to assess whether there was an absolute requirement for MHC class I expression and/or CD8+ T-cells in diabetogenesis. These NOD-B2mnull mice do not express cell surface MHC class I molecules or produce detectable levels of CD8+ T-cells and are diabetes and insulitis resistant. Previous results from transgenic mouse models indicated that intracellular accumulation of MHC class I molecules negatively affects pancreatic beta-cell function and can result in the development of nonautoimmune insulin-dependent diabetes mellitus (IDDM). MHC class I molecules have been shown to accumulate intracellularly in the presence of a disrupted B2m locus, but this mutation does not negatively affect plasma insulin levels in either NOD/Lt mice or in those of a mixed 129 and C57BL/6 genetic background. Interestingly, 14% of the male mice in this mixed background did develop hyperinsulinemia (> 1,500 pM) independent of the disrupted B2m locus, suggesting that these mice could conceivably develop insulin-resistant diabetes. However, none of these mice became diabetic at up to 22 months of age. Thus, elimination of cell surface MHC class I expression with a disrupted B2m gene blocks autoimmune diabetes in NOD/Lt mice, without engendering a separate, distinct form of glucose intolerance.

Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A convergently regulate the synaptic ratio of ionotropic glutamate receptor subclasses.

PubMed

Pan, Luyuan; Broadie, Kendal S

2007-11-07

A current hypothesis proposes that fragile X mental retardation protein (FMRP), an RNA-binding translational regulator, acts downstream of glutamatergic transmission, via metabotropic glutamate receptor (mGluR) G(q)-dependent signaling, to modulate protein synthesis critical for trafficking ionotropic glutamate receptors (iGluRs) at synapses. However, direct evidence linking FMRP and mGluR function with iGluR synaptic expression is limited. In this study, we use the Drosophila fragile X model to test this hypothesis at the well characterized glutamatergic neuromuscular junction (NMJ). Two iGluR classes reside at this synapse, each containing common GluRIIC (III), IID and IIE subunits, and variable GluRIIA (A-class) or GluRIIB (B-class) subunits. In Drosophila fragile X mental retardation 1 (dfmr1) null mutants, A-class GluRs accumulate and B-class GluRs are lost, whereas total GluR levels do not change, resulting in a striking change in GluR subclass ratio at individual synapses. The sole Drosophila mGluR, DmGluRA, is also expressed at the NMJ. In dmGluRA null mutants, both iGluR classes increase, resulting in an increase in total synaptic GluR content at individual synapses. Targeted postsynaptic dmGluRA overexpression causes the exact opposite GluR phenotype to the dfmr1 null, confirming postsynaptic GluR subtype-specific regulation. In dfmr1; dmGluRA double null mutants, there is an additive increase in A-class GluRs, and a similar additive impact on B-class GluRs, toward normal levels in the double mutants. These results show that both dFMRP and DmGluRA differentially regulate the abundance of different GluR subclasses in a convergent mechanism within individual postsynaptic domains.

20 CFR 416.1013 - Disability determinations the State makes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Disability Determination Function § 416.1013 Disability determinations the State makes. (a) General rule. A... § 416.903(d)(1). (b) New classes of cases. Where any new class or classes of cases arise requiring... disability determinations. We will provide the State with the necessary funding to do the additional work. (c...

20 CFR 404.1613 - Disability determinations the State makes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Disability Determination Function § 404.1613 Disability determinations the State makes. (a) General rule. A... § 404.1503(d)(1). (b) New classes of cases. Where any new class or classes of cases arise requiring... disability determinations. We will provide the State with the necessary funding to do the additional work. (c...

Switch Transcripts in Immunoglobulin Class Switching

NASA Astrophysics Data System (ADS)

Lorenz, Matthias; Jung, Steffen; Radbruch, Andreas

1995-03-01

B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG1) by the heterologous human metallothionein II_A promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.

Epigenetic Mechanisms Regulate MHC and Antigen Processing Molecules in Human Embryonic and Induced Pluripotent Stem Cells

PubMed Central

Suárez-Álvarez, Beatriz; Rodriguez, Ramón M.; Calvanese, Vincenzo; Blanco-Gelaz, Miguel A.; Suhr, Steve T.; Ortega, Francisco; Otero, Jesus; Cibelli, Jose B.; Moore, Harry; Fraga, Mario F.; López-Larrea, Carlos

2010-01-01

Background Human embryonic stem cells (hESCs) are an attractive resource for new therapeutic approaches that involve tissue regeneration. hESCs have exhibited low immunogenicity due to low levels of Mayor Histocompatibility Complex (MHC) class-I and absence of MHC class-II expression. Nevertheless, the mechanisms regulating MHC expression in hESCs had not been explored. Methodology/Principal Findings We analyzed the expression levels of classical and non-classical MHC class-I, MHC class-II molecules, antigen-processing machinery (APM) components and NKG2D ligands (NKG2D-L) in hESCs, induced pluripotent stem cells (iPSCs) and NTera2 (NT2) teratocarcinoma cell line. Epigenetic mechanisms involved in the regulation of these genes were investigated by bisulfite sequencing and chromatin immunoprecipitation (ChIP) assays. We showed that low levels of MHC class-I molecules were associated with absent or reduced expression of the transporter associated with antigen processing 1 (TAP-1) and tapasin (TPN) components in hESCs and iPSCs, which are involved in the transport and load of peptides. Furthermore, lack of β2-microglobulin (β2m) light chain in these cells limited the expression of MHC class I trimeric molecule on the cell surface. NKG2D ligands (MICA, MICB) were observed in all pluripotent stem cells lines. Epigenetic analysis showed that H3K9me3 repressed the TPN gene in undifferentiated cells whilst HLA-B and β2m acquired the H3K4me3 modification during the differentiation to embryoid bodies (EBs). Absence of HLA-DR and HLA-G expression was regulated by DNA methylation. Conclusions/Significance Our data provide fundamental evidence for the epigenetic control of MHC in hESCs and iPSCs. Reduced MHC class I and class II expression in hESCs and iPSCs can limit their recognition by the immune response against these cells. The knowledge of these mechanisms will further allow the development of strategies to induce tolerance and improve stem cell allograft acceptance. PMID:20419139

HLA class I associations with EBV+ post-transplant lymphoproliferative disorder.

PubMed

Jones, Kimberley; Wockner, Leesa; Thornton, Alycia; Gottlieb, David; Ritchie, David S; Seymour, John F; Kumarasinghe, Gayathri; Gandhi, Maher K

2015-03-01

Epstein-Barr virus (EBV) is frequently associated with post-transplant lymphoproliferative disorders (EBV(+) PTLD). In these cases, impaired Epstein-Barr virus (EBV)-specific CD8(+) T-cell immunity is strongly implicated and antigen presentation within the malignant B-cell is intact. Interestingly, several studies have reported HLA class I alleles with protective or susceptibility associations. However, results are conflicting, likely influenced by methodology including inconsistent use of multiple hypothesis testing. By contrast, HLA class I associations have been repeatedly reported for classical Hodgkin Lymphoma (cHL), in which EBV is also implicated in a proportion of cases. In contrast to EBV(+) PTLD which expresses the immunodominant EBV latency III EBNA3A/B/C proteins, EBV(+) cHL is restricted to the subdominant EBNA1/LMP1/LMP2 proteins. Herein, we report a study of HLA class I associations in EBV(+) PTLD, with 263 patients with lymphoma (cHL or PTLD) evaluated. Two Australian population cohorts, n = 23,736 and n = 891 were used for comparison. Contrary to previous reports, no HLA class I associations with EBV(+) PTLD were found, whereas for cHL known HLA class I associations were confirmed, with HLA-A*02 homozygous individuals having the lowest odds of developing EBV(+) cHL. Our results suggest that HLA class I does not influence susceptibility to the viral latency III expressing lymphoma, EBV(+) PTLD. Further studies are required for definitive confirmation. Copyright © 2015. Published by Elsevier B.V.

B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.

PubMed

Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L; Wang, Rui; Xu, Zhenming; Casali, Paolo

2015-02-01

Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS-mediated long-term primary class-switched antibody responses and memory-like antibody responses in vivo and induced generation of class-switched B cells and plasma cells in vitro. Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety. In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand. In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression. The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154. Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154. Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.

B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses

PubMed Central

Pone, Egest J.; Lou, Zheng; Lam, Tonika; Greenberg, Milton L.; Wang, Rui; Xu, Zhenming; Casali, Paolo

2015-01-01

Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS mediated long-term primary class-switched antibody responses and memory-like antibody responses in vivo and induced generation of class-switched B cells and plasma cells in vitro. Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety. In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand. In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression. The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154. Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154. Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines. PMID:25536171

Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE

PubMed Central

Wu, Yee Ling; Teichmann, Sarah A.

2017-01-01

Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4–induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma. PMID:27994069

The D0 immunoglobulin-like domain plays a central role for the stronger binding of KIR3DL2 to B27 free heavy chain dimers

PubMed Central

Hatano, Hiroko; Shaw, Jacqueline; Marquardt, Kaitlin; Zhang, Zhiyong; Gauthier, Laurent; Chanteux, Stephanie; Rossi, Benjamin; Li, Demin; Mitchell, Julie; Kollnberger, Simon

2015-01-01

We have proposed that the killer cell immunoglobulin-like receptor KIR3DL2 binding more strongly to HLA-B27 (B27) β2m-free heavy chain (FHC) dimers regulates lymphocyte function in arthritis and infection. We compared the function of B27 FHC dimers with other class I heavy chains and identified contact residues in KIR3DL2. B27 FHC dimers interacted functionally with KIR3DL2 on NK and reporter cells more strongly than other class I FHC. Mutagenesis identified key residues in the D0 and other immunoglobulin-like domains which were shared and distinct from KIR3DL1, for KIR3DL2 binding to B27 and other class I FHC. We modeled B27 dimer binding to KIR3DL2 and compared experimental mutagenesis data with computational “hot spot” predictions. Modelling predicts the stronger binding of B27 dimers to KIR3DL2 is mediated by non-symmetrical complementary contacts of the D0 and D1 domains with the α1, α2 and α3 domains of both B27 heavy chains. By contrast, the D2 domain primarily contacts residues in the α2 domain of one B27 heavy chain. These findings both provide novel insights about the molecular basis of KIR3DL2 binding to HLA-B27 and other ligands and suggest an important role for KIR3DL2 HLA-B27 interactions in controlling the function of NK cells in HLA-B27+ individuals. PMID:25582852

49 CFR 176.176 - Signals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Signals. 176.176 Section 176.176 Transportation... Class 1 (Explosive) Materials Handling Class 1 (explosive) Materials in Port § 176.176 Signals. When... exhibit the following signals: (a) By day, flag “B” (Bravo) of the international code of signals; and (b...

49 CFR 176.176 - Signals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Signals. 176.176 Section 176.176 Transportation... Class 1 (Explosive) Materials Handling Class 1 (explosive) Materials in Port § 176.176 Signals. When... exhibit the following signals: (a) By day, flag “B” (Bravo) of the international code of signals; and (b...

46 CFR 114.400 - Definitions of terms used in this subchapter.

Code of Federal Regulations, 2010 CFR

2010-10-01

... only at an approved A-Class or B-Class bulkhead. Control space (1) means a space containing: (1) An...; (3) Centralized fire control or detection equipment, such as fixed gas extinguishing system controls; or (4) Machinery controls not located within a machinery space. Corrosion-resistant material or...

46 CFR 114.400 - Definitions of terms used in this subchapter.

Code of Federal Regulations, 2012 CFR

2012-10-01

... only at an approved A-Class or B-Class bulkhead. Control space (1) means a space containing: (1) An...; (3) Centralized fire control or detection equipment, such as fixed gas extinguishing system controls; or (4) Machinery controls not located within a machinery space. Corrosion-resistant material or...

49 CFR 176.176 - Signals.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Signals. 176.176 Section 176.176 Transportation... Class 1 (Explosive) Materials Handling Class 1 (explosive) Materials in Port § 176.176 Signals. When... exhibit the following signals: (a) By day, flag “B” (Bravo) of the international code of signals; and (b...

49 CFR 176.176 - Signals.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Signals. 176.176 Section 176.176 Transportation... Class 1 (Explosive) Materials Handling Class 1 (explosive) Materials in Port § 176.176 Signals. When... exhibit the following signals: (a) By day, flag “B” (Bravo) of the international code of signals; and (b...

49 CFR 176.176 - Signals.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Signals. 176.176 Section 176.176 Transportation... Class 1 (Explosive) Materials Handling Class 1 (explosive) Materials in Port § 176.176 Signals. When... exhibit the following signals: (a) By day, flag “B” (Bravo) of the international code of signals; and (b...

Data for polarization in charmless B{yields}{phi}K*: A signal for new physics?

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

Das, Prasanta Kumar; Yang, K.-C.

2005-05-01

The recent observations of sizable transverse fractions of B{yields}{phi}K* may hint for the existence of new physics. We analyze all possible new-physics four-quark operators and find that two classes of new-physics operators could offer resolutions to the B{yields}{phi}K* polarization anomaly. The operators in the first class have structures (1-{gamma}{sub 5})x(1-{gamma}{sub 5}), {sigma}(1-{gamma}{sub 5})x{sigma}(1-{gamma}{sub 5}), and in the second class (1+{gamma}{sub 5})x(1+{gamma}{sub 5}), {sigma}(1+{gamma}{sub 5})x{sigma}(1+{gamma}{sub 5}). For each class, the new-physics effects can be lumped into a single parameter. Two possible experimental results of polarization phases, arg(A{sub perpendicular})-arg(A{sub parallel}){approx_equal}{pi} or 0, originating from the phase ambiguity in data, could be separatelymore » accounted for by our two new-physics scenarios: the first (second) scenario with the first (second) class new-physics operators. The consistency between the data and our new-physics analysis suggests a small new-physics weak phase, together with a large(r) strong phase. We obtain sizable transverse fractions {lambda}{sub parallel{sub parallel}}+{lambda}{sub perpendicular{sub perpendicular}}{approx_equal}{lambda}{sub 00}, in accordance with the observations. We find {lambda}{sub parallel{sub parallel}}{approx_equal}0.8{lambda}{sub perpendicular{sub perpendicular}} in the first scenario but {lambda}{sub parallel{sub parallel}} > or approx. {lambda}{sub perpendicular{sub perpendicular}} in the second scenario. We discuss the impact of the new-physics weak phase on observations.« less

Results of a systematic literature review of treatment modalities for jugulotympanic paraganglioma, stratified per Fisch class.

PubMed

Jansen, T T G; Timmers, H J L M; Marres, H A M; Kaanders, J H A M; Kunst, H P M

2018-04-01

Key for successful jugulotympanic paraganglioma management is a personalised approach aiming for the best practice for each individual patient. To this end, a systematic review is performed, evaluating the local control and complication rates for the different treatment modalities stratified by the broadly accepted Fisch classification. A systematic literature review according to the PRISMA statement was performed. A detailed overview of individual treatment outcomes per Fisch class is provided. Local control, cranial nerve damage, complications, function recovery. Eighteen studies were selected, resembling 83 patients treated with radiotherapy and 299 with surgery. Excellent local control was found post-surgery for class A and B tumours, and risk of cranial nerve damage was <1%. For class C1-4 tumours, local control was 80%-95% post-surgery (84% post-radiotherapy), and cranial nerve damage was found in 71%-76% (none post-radiotherapy; P < .05). There was no difference in treatment outcomes between tumours of different C class. For class C1-4De/Di tumours, local control was 38%-86% (98% post-radiotherapy; P < .05) and cranial nerve damage/complication rates were 67%-100% (3% post-radiotherapy; P < .05). C1-4DeDi tumours showed lesser local control and cranial nerve damage rates when compared to C1-4De tumours. An individual risk is constituted for surgery and radiotherapy, stratified per Fisch class. For class A and B tumours, surgery is a suitable treatment option. For class C and D tumours, radiotherapy results in lower complication rates and similar or better local control rates when compared to the surgical group. © 2017 John Wiley & Sons Ltd.

Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes

PubMed Central

2013-01-01

Background The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef’s most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. Results Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naïve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p < 0.0001) than clones from other subtypes. Subtype C Nefs displayed the lowest in vitro functionality. Inter-subtype differences in HLA class I downregulation remained statistically significant after controlling for differences in age, sex, and clinical parameters (p < 0.0001). The synthesized consensus subtype B Nef showed higher activities compared to consensus C Nef, which was most pronounced in cells expressing lower protein levels. Nef clones exhibited substantial inter-subtype diversity: cohort consensus residues differed at 25% of codons, while a similar proportion of codons exhibited substantial inter-subtype differences in major variant frequency. These amino acids, along with others identified in intra-subtype analyses, represent candidates for mediating inter-subtype differences in Nef function. Conclusions Results support a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation. PMID:24041011

Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs.

PubMed

Murakami, S; Takayama, S; Kitamura, M; Shimabukuro, Y; Yanagi, K; Ikezawa, K; Saho, T; Nozaki, T; Okada, H

2003-02-01

Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.

The use of computer simulations in whole-class versus small-group settings

NASA Astrophysics Data System (ADS)

Smetana, Lara Kathleen

This study explored the use of computer simulations in a whole-class as compared to small-group setting. Specific consideration was given to the nature and impact of classroom conversations and interactions when computer simulations were incorporated into a high school chemistry course. This investigation fills a need for qualitative research that focuses on the social dimensions of actual classrooms. Participants included a novice chemistry teacher experienced in the use of educational technologies and two honors chemistry classes. The study was conducted in a rural school in the south-Atlantic United States at the end of the fall 2007 semester. The study took place during one instructional unit on atomic structure. Data collection allowed for triangulation of evidence from a variety of sources approximately 24 hours of video- and audio-taped classroom observations, supplemented with the researcher's field notes and analytic journal; miscellaneous classroom artifacts such as class notes, worksheets, and assignments; open-ended pre- and post-assessments; student exit interviews; teacher entrance, exit and informal interviews. Four web-based simulations were used, three of which were from the ExploreLearning collection. Assessments were analyzed using descriptive statistics and classroom observations, artifacts and interviews were analyzed using Erickson's (1986) guidelines for analytic induction. Conversational analysis was guided by methods outlined by Erickson (1982). Findings indicated (a) the teacher effectively incorporated simulations in both settings (b) students in both groups significantly improved their understanding of the chemistry concepts (c) there was no statistically significant difference between groups' achievement (d) there was more frequent exploratory talk in the whole-class group (e) there were more frequent and meaningful teacher-student interactions in the whole-class group (f) additional learning experiences not measured on the assessment resulted from conversations and interactions in the whole-class setting (g) the potential benefits of exploratory talk in the whole-class setting were not fully realized. These findings suggest that both whole-class and small-group settings are appropriate for using computer simulations in science. The effective incorporation of simulations into whole-class instruction may provide a solution to the dilemma of technology penetration versus integration in today's classrooms.

Negatively Cooperative Binding of High Density Lipoprotein to the HDL Receptor SR-BI†

PubMed Central

Nieland, Thomas J.F.; Xu, Shangzhe; Penman, Marsha; Krieger, Monty

2011-01-01

Scavenger receptor class B, type I (SR-BI) is a high-density lipoprotein (HDL) receptor, which also binds low density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a co-receptor for hepatitis C virus and a signaling receptor that regulates cell metabolism. Many investigators have reported that lipoproteins bind to SR-BI via a single class of independent (not interacting), high affinity binding sites (one site model). We have re-investigated the ligand concentration dependence of 125I-HDL binding to SR-BI and SR-BI-mediated specific uptake of [3H]CE from [3H]CE-HDL using an expanded range of ligand concentrations (<1 µg protein/ml, lower than previously reported). Scatchard and non-linear least squares model fitting analyses of the binding and uptake data were both inconsistent with a single class of independent binding sites binding univalent lipoprotein ligands. The data are best fit by models in which SR-BI has either two independent classes of binding sites, or one class of sites exhibiting negative cooperativity due to either classic allostery or ensemble effects (‘ lattice model’). Similar results were observed for LDL. Application of the ‘infinite dilution’ dissociation rate method established that the binding of 125I-HDL to SR-BI at 4 °C exhibits negative cooperativity. The unexpected complexity of the interactions of lipoproteins with SR-BI should be taken into account when interpreting the results of experiments that explore the mechanism(s) by which SR-BI mediates ligand binding, lipid transport and cell signaling. PMID:21254782

77 FR 49712 - Amendment to Class B Airspace; Salt Lake City, UT

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

... operating in the vicinity of SLC. The modified Class B airspace areas were designed to ensure all instrument... final Salt Lake City Class B airspace design provides operational and safety benefits to all airspace... Salt Lake City Class B airspace design also incorporated reductions to the northern and southern...

Exploring When and Why to Use Arabic in the Saudi Arabian EFL Classroom: Viewing L1 Use as Eclectic Technique

ERIC Educational Resources Information Center

Khresheh, Asim

2012-01-01

This study aims to investigate when and why to use Arabic as L1 in the Saudi Arabian EFL classroom. For this purpose, 45 classroom observations were performed for beginning, intermediate, and advanced levels of students. 5 classes were chosen randomly for each level and each class was observed three times. Based on the classroom observations,…

Mechanisms regulating enhanced HLA class II-mediated CD4+ T cell recognition of human B-cell lymphoma by resveratrol

PubMed Central

RADWAN, FAISAL F. Y.; ZHANG, LIXIA; HOSSAIN, AZIM; DOONAN, BENTLY P.; GOD, JASON; HAQUE, AZIZUL

2015-01-01

Malignant B-cells express measurable levels of HLA class II proteins, but often escape immune recognition by CD4+ T cells. Resveratrol (Resv) has been the focus of numerous investigations due to its potential chemopreventive and anti-cancer effects, but it has never been tested in the regulation of immune components in B-cell tumors. Here, we show for the first time that Resv treatment enhances HLA class II-mediated immune detection of B-cell lymphomas by altering immune components and class II presentation in tumor cells. Resv treatment induced an upregulation of both classical and non-classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT), increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and their subsequent recognition by CD4+ T cells. Mechanistic study demonstrated that Resv treatment activated the recycling class II pathway of Ag presentation through upregulation of Rab 4B protein expression in B-lymphoma cells. These findings suggest that HLA class II-mediated immune recognition of malignant B-cells can be improved by Resv treatment, thus encouraging its potential use in chemoimmunotherapy of B-cell lymphoma. PMID:21854084

Functional design criteria for interim stabilization safety class 1 trip circuit

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

Larson, R.E., Westinghouse Hanford

1996-06-10

This Functional Design Criteria document outlines the basic requirements for the Safety Class 1 Trip Circuit. The objective of the Safety Class 1 Trip Circuit is to isolate the power circuitry to the Class 1 Division 2, Group B or lesser grade electrically fed loads located in the pump pit. The electrically fed load circuits need to have power isolated to them upon receipt of the following conditions, loss of flammable gases being released (above a predetermined threshold), and seismic(greater than 0.12g acceleration) activity. The two circuits requiring power isolation are the pump and heat trace power circuits. The Safetymore » Class 1 Trip Circuit will be used to support salt well pumping in SST`s containing potentially flammable gas-bearing / gas-producing radioactive waste.« less

The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove

PubMed Central

Tang, Minzhong; Lautenberger, James A.; Gao, Xiaojiang; Sezgin, Efe; Hendrickson, Sher L.; Troyer, Jennifer L.; David, Victor A.; Guan, Li; Mcintosh, Carl E.; Guo, Xiuchan; Zheng, Yuming; Liao, Jian; Deng, Hong; Malasky, Michael; Kessing, Bailey; Winkler, Cheryl A.; Carrington, Mary; dé The, Guy; Zeng, Yi; O'Brien, Stephen J.

2012-01-01

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6.8×10−8 respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China. PMID:23209447

Patterns and predictors of violence against children in Uganda: a latent class analysis

PubMed Central

Clarke, Kelly; Patalay, Praveetha; Allen, Elizabeth; Knight, Louise; Naker, Dipak; Devries, Karen

2016-01-01

Objective To explore patterns of physical, emotional and sexual violence against Ugandan children. Design Latent class and multinomial logistic regression analysis of cross-sectional data. Setting Luwero District, Uganda. Participants In all, 3706 primary 5, 6 and 7 students attending 42 primary schools. Main outcome and measure To measure violence, we used the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool—Child Institutional. We used the Strengths and Difficulties Questionnaire to assess mental health and administered reading, spelling and maths tests. Results We identified three violence classes. Class 1 (N=696 18.8%) was characterised by emotional and physical violence by parents and relatives, and sexual and emotional abuse by boyfriends, girlfriends and unrelated adults outside school. Class 2 (N=975 26.3%) was characterised by physical, emotional and sexual violence by peers (male and female students). Children in Classes 1 and 2 also had a high probability of exposure to emotional and physical violence by school staff. Class 3 (N=2035 54.9%) was characterised by physical violence by school staff and a lower probability of all other forms of violence compared to Classes 1 and 2. Children in Classes 1 and 2 were more likely to have worked for money (Class 1 Relative Risk Ratio 1.97, 95% CI 1.54 to 2.51; Class 2 1.55, 1.29 to 1.86), been absent from school in the previous week (Class 1 1.31, 1.02 to 1.67; Class 2 1.34, 1.10 to 1.63) and to have more mental health difficulties (Class 1 1.09, 1.07 to 1.11; Class 2 1.11, 1.09 to 1.13) compared to children in Class 3. Female sex (3.44, 2.48 to 4.78) and number of children sharing a sleeping area predicted being in Class 1. Conclusions Childhood violence in Uganda forms distinct patterns, clustered by perpetrator and setting. Research is needed to understand experiences of victimised children, and to develop mental health interventions for those with severe violence exposures. Trial registration number NCT01678846; Results. PMID:27221125

Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

PubMed

Halperin, John J; Kurlan, Roger; Schwalb, Jason M; Cusimano, Michael D; Gronseth, Gary; Gloss, David

2015-12-08

We evaluated evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness. We identified and classified relevant published studies according to 2004 and 2011 American Academy of Neurology methodology. Of 21 articles, we identified 3 Class I articles. Shunting is possibly effective in iNPH (96% chance subjective improvement, 83% chance improvement on timed walk test at 6 months) (3 Class III). Serious adverse event risk was 11% (1 Class III). Predictors of success included elevated Ro (1 Class I, multiple Class II), impaired cerebral blood flow reactivity to acetazolamide (by SPECT) (1 Class I), and positive response to either external lumbar drainage (1 Class III) or repeated lumbar punctures. Age may not be a prognostic factor (1 Class II). Data are insufficient to judge efficacy of radionuclide cisternography or aqueductal flow measurement by MRI. Clinicians may choose to offer shunting for subjective iNPH symptoms and gait (Level C). Because of significant adverse event risk, risks and benefits should be carefully weighed (Level B). Clinicians should inform patients with iNPH with elevated Ro and their families that they have an increased chance of responding to shunting compared with those without such elevation (Level B). Clinicians may counsel patients with iNPH and their families that (1) positive response to external lumbar drainage or to repeated lumbar punctures increases the chance of response to shunting, and (2) increasing age does not decrease the chance of shunting being successful (both Level C). © 2015 American Academy of Neurology.

Silencing or inhibition of endoplasmic reticulum aminopeptidase 1 (ERAP1) suppresses free heavy chain expression and Th17 responses in ankylosing spondylitis

PubMed Central

Chen, Liye; Ridley, Anna; Hammitzsch, Ariane; Al-Mossawi, Mohammad Hussein; Bunting, Helen; Georgiadis, Dimitris; Chan, Antoni; Kollnberger, Simon; Bowness, Paul

2016-01-01

Objective Human leucocyte antigen (HLA)-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly associated with ankylosing spondylitis (AS). ERAP1 is a key aminopeptidase in HLA class I presentation and can potentially alter surface expression of HLA-B27 free heavy chains (FHCs). We studied the effects of ERAP1 silencing/inhibition/variations on HLA-B27 FHC expression and Th17 responses in AS. Methods Flow cytometry was used to measure surface expression of HLA class I in peripheral blood mononuclear cells (PBMCs) from patients with AS carrying different ERAP1 genotypes (rs2287987, rs30187 and rs27044) and in ERAP1-silenced/inhibited/mutated HLA-B27-expressing antigen presenting cells (APCs). ERAP1-silenced/inhibited APCs were cocultured with KIR3DL2CD3ε-reporter cells or AS CD4+ T cells. Th17 responses of AS CD4+ T cells were measured by interleukin (IL)-17A ELISA and Th17 intracellular cytokine staining. FHC cell surface expression and Th17 responses were also measured in AS PBMCs following ERAP1 inhibition. Results The AS-protective ERAP1 variants, K528R and Q730E, were associated with reduced surface FHC expression by monocytes from patients with AS and HLA-B27-expressing APCs. ERAP1 silencing or inhibition in APCs downregulated HLA-B27 FHC surface expression, reduced IL-2 production by KIR3DL2CD3ε-reporter cells and suppressed the Th17 expansion and IL-17A secretion by AS CD4+ T cells. ERAP1 inhibition of AS PBMCs reduced HLA class I FHC surface expression by monocytes and B cells, and suppressed Th17 expansion. Conclusions ERAP1 activity determines surface expression of HLA-B27 FHCs and potentially promotes Th17 responses in AS through binding of HLA-B27 FHCs to KIR3DL2. Our data suggest that ERAP1 inhibition has potential for AS treatment. PMID:26130142

ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

2010-01-01

SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

KIR3DL2 binds to HLA-B27 dimers and free heavy chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis

PubMed Central

Wong-Baeza, Isabel; Ridley, Anna; Shaw, Jackie; Hatano, Hiroko; Rysnik, Oliwia; McHugh, Kirsty; Piper, Christopher; Brackenbridge, Simon; Fernandes, Ricardo; Chan, Anthoni; Bowness, Paul; Kollnberger, Simon

2013-01-01

1Abstract The Human Leukocyte Antigen HLA-B27(B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of antigen presenting cells (APC) as both classical β2m-associated B27 and as B27 free heavy chain forms (FHC) including disulphide-bonded heavy chain homodimers (termed B272). B27 FHC forms but not classical B27 bind to KIR3DL2. HLA-A3 which is not associated with spondyloarthritis (SpA) is also a ligand for KIR3DL2. Here we show that B272 and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B272 tetramers bound KIR3DL2 transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27-transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric and monomeric free heavy chains from HLA-B27 expressing cell lines. Binding to B272 and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B272 and B27 FHC stimulated KIR3DL2CD3ε–transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFNγ secretion and promoted greater survival of KIR3DL2+CD4 T and NK cells than binding to other HLA-class I. KIR3DL2+ T cells from B27+SpA patients proliferated more in response to antigen presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27+ SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC. PMID:23440420

Ozone-induced gene expression occurs via ethylene-dependent and -independent signalling.

PubMed

Grimmig, Bernhard; Gonzalez-Perez, Maria N; Leubner-Metzger, Gerhard; Vögeli-Lange, Regina; Meins, Fred; Hain, Rüdiger; Penuelas, Josep; Heidenreich, Bernd; Langebartels, Christian; Ernst, Dieter; Sandermann, Heinrich

2003-03-01

Recent studies suggest that ethylene is involved in signalling ozone-induced gene expression. We show here that application of ozone increased glucuronidase (GUS) expression of chimeric reporter genes regulated by the promoters of the tobacco class I beta-1,3-glucanases (GLB and Gln2) and the grapevine resveratrol synthase (Vst1) genes in transgenic tobacco leaves. 5'-deletion analysis of the class I beta-1,3-glucanase promoter revealed that ozone-induced gene regulation is mainly mediated by the distal enhancer region containing the positively acting ethylene-responsive element (ERE). In addition, application of 1-methylcyclopropene (1-MCP), an inhibitor of ethylene action, blocked ozone-induced class I beta-1,3-glucanase promoter activity. Enhancer activity and ethylene-responsiveness depended on the integrity of the GCC boxes, cis-acting elements present in the ERE of the class I beta-1,3-glucanase and the basic-type pathogenesis-related PR-1 protein (PRB-1b) gene promoters. The minimal PRB-1b promoter containing only the ERE with intact GCC boxes, was sufficient to confer 10-fold ozone inducibility to a GUS-reporter gene, while a substitution mutation in the GCC box abolished ozone responsiveness. The ERE region of the class I beta-1,3-glucanase promoter containing two intact GCC boxes confered strong ozone inducibility to a minimal cauliflower mosaic virus (CaMV) 35S RNA promoter, whereas two single-base substitution in the GCC boxes resulted in a complete loss of ozone inducibility. Taken together, these datastrongly suggest that ethylene is signalling ozone-induced expression of class I beta-l,3-glucanase and PRB-1b genes. Promoter analysis of the stilbene synthase Vst1 gene unravelled different regions for ozone and ethylene-responsiveness. Application of 1-MCP blocked ethylene-induced Vst1 induction, but ozone induction was not affected. This shows that ozone-induced gene expression occurs via at least two different signalling mechanisms and suggests an additional ethylene independent signalling pathway for ozone-induced expression of genes involved in phytoalexin biosynthesis.

A genetic study of Wilson’s disease in the United Kingdom

PubMed Central

Coffey, Alison J.; Durkie, Miranda; Hague, Stephen; McLay, Kirsten; Emmerson, Jennifer; Lo, Christine; Klaffke, Stefanie; Joyce, Christopher J.; Dhawan, Anil; Hadzic, Nedim; Mieli-Vergani, Giorgina; Kirk, Richard; Elizabeth Allen, K.; Nicholl, David; Wong, Siew; Griffiths, William; Smithson, Sarah; Giffin, Nicola; Taha, Ali; Connolly, Sally; Gillett, Godfrey T.; Tanner, Stuart; Bonham, Jim; Sharrack, Basil; Palotie, Aarno; Rattray, Magnus; Dalton, Ann

2013-01-01

Previous studies have failed to identify mutations in the Wilson’s disease gene ATP7B in a significant number of clinically diagnosed cases. This has led to concerns about genetic heterogeneity for this condition but also suggested the presence of unusual mutational mechanisms. We now present our findings in 181 patients from the United Kingdom with clinically and biochemically confirmed Wilson’s disease. A total of 116 different ATP7B mutations were detected, 32 of which are novel. The overall mutation detection frequency was 98%. The likelihood of mutations in genes other than ATP7B causing a Wilson’s disease phenotype is therefore very low. We report the first cases with Wilson’s disease due to segmental uniparental isodisomy as well as three patients with three ATP7B mutations and three families with Wilson’s disease in two consecutive generations. We determined the genetic prevalence of Wilson’s disease in the United Kingdom by sequencing the entire coding region and adjacent splice sites of ATP7B in 1000 control subjects. The frequency of all single nucleotide variants with in silico evidence of pathogenicity (Class 1 variant) was 0.056 or 0.040 if only those single nucleotide variants that had previously been reported as mutations in patients with Wilson’s disease were included in the analysis (Class 2 variant). The frequency of heterozygote, putative or definite disease-associated ATP7B mutations was therefore considerably higher than the previously reported occurrence of 1:90 (or 0.011) for heterozygote ATP7B mutation carriers in the general population (P < 2.2 × 10-16 for Class 1 variants or P < 5 × 10-11 for Class 2 variants only). Subsequent exclusion of four Class 2 variants without additional in silico evidence of pathogenicity led to a further reduction of the mutation frequency to 0.024. Using this most conservative approach, the calculated frequency of individuals predicted to carry two mutant pathogenic ATP7B alleles is 1:7026 and thus still considerably higher than the typically reported prevalence of Wilson’s disease of 1:30 000 (P = 0.00093). Our study provides strong evidence for monogenic inheritance of Wilson’s disease. It also has major implications for ATP7B analysis in clinical practice, namely the need to consider unusual genetic mechanisms such as uniparental disomy or the possible presence of three ATP7B mutations. The marked discrepancy between the genetic prevalence and the number of clinically diagnosed cases of Wilson’s disease may be due to both reduced penetrance of ATP7B mutations and failure to diagnose patients with this eminently treatable disorder. PMID:23518715

Genetic engineering of Streptomyces bingchenggensis to produce milbemycins A3/A4 as main components and eliminate the biosynthesis of nanchangmycin.

PubMed

Zhang, Ji; An, Jing; Wang, Ji-Jia; Yan, Yi-Jun; He, Hai-Rong; Wang, Xiang-Jing; Xiang, Wen-Sheng

2013-12-01

Milbemycins A3/A4 are important 16-membered macrolides which have been commercialized and widely used as pesticide and veterinary medicine. However, similar to other milbemycin producers, the production of milbemycins A3/A4 in Streptomyces bingchenggensis is usually accompanied with undesired by-products such as C5-O - methylmilbemycins B2/B3 (α-class) and β1/β2 (β-class) together with nanchangmycin. In order to obtain high yield milbemycins A3/A4-producing strains that produce milbemycins A3/A4 as main components, milD, a putative C5-O-methyltransferase gene of S. bingchenggensis , was biofunctionally investigated by heterologous expression in Escherichia coli . Enzymatic analysis indicated that MilD can catalyze both α-class (A3/A4) and β-class milbemycins (β11) into C5-O-methylmilbemycins B2/B3 and β1, respectively, suggesting little effect of furan ring formed between C6 and C8a on the C5-O-methylation catalyzed by MilD. Deletion of milD gene resulted in the elimination of C5-Omethylmilbemycins B2/B3 and β1/β2 together with an increased yield of milbemycins A3/A4 in disruption strain BCJ13. Further disruption of the gene nanLD encoding loading module of polyketide synthase responsible for the biosynthesis of nanchangmycin led to strain BCJ36 that abolished the production of nanchangmycin. Importantly, mutant strain BCJ36 (ΔmilDΔnanLD) produced milbemycins A3/A4 as main secondary metabolites with a yield of 2312 ± 47 μg/ml, which was approximately 74 % higher than that of the initial strain S. bingchenggensis BC-109-6 (1326 ± 37 μg/ml).

YY1 Controls Immunoglobulin Class Switch Recombination and Nuclear Activation-Induced Deaminase Levels

PubMed Central

Zaprazna, Kristina

2012-01-01

Activation-induced deaminase (AID) is an enzyme required for class switch recombination (CSR) and somatic hypermutation (SHM), processes that ensure antibody maturation and expression of different immunoglobulin isotypes. AID function is tightly regulated by tissue- and stage-specific expression, nuclear localization, and protein stability. Transcription factor YY1 is crucial for early B cell development, but its function at late B cell stages is unknown. Here, we show that YY1 conditional knockout in activated splenic B cells interferes with CSR. Knockout of YY1 did not affect B cell proliferation, transcription of the AID and IgM genes, or levels of various switch region germ line transcripts. However, we show that YY1 physically interacts with AID and controls the accumulation of nuclear AID, at least in part, by increasing nuclear AID stability. We show for the first time that YY1 plays a novel role in CSR and controls nuclear AID protein levels. PMID:22290437

49 CFR 213.121 - Rail joints.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the rail on which it is applied. (b) If a joint bar on Classes 3 through 5 track is cracked, broken... at each joint in Classes 2 through 5 track, and with at least one bolt in Class 1 track. (e) In the... accommodate expansion and contraction due to temperature variations. When no-slip, joint-to-rail contact...

40 CFR 82.17 - Apportionment of baseline production allowances for class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... allowances for class II controlled substances. 82.17 Section 82.17 Protection of Environment ENVIRONMENTAL... Consumption Controls § 82.17 Apportionment of baseline production allowances for class II controlled... 1,759,681 MDA Manufacturing HCFC-22 2,383,835 Solvay Solexis HCFC-142b 6,541,764 [ 74 FR 66446, Dec...

40 CFR 2.207 - Class determinations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Confidentiality of Business Information § 2.207 Class determinations. (a) The General Counsel may make and issue a... items of business information; (2) One or more characteristics common to all such items of information... § 2.204(b)(1), § 2.204(d), § 2.205(d), or § 2.206. However, the existence of a class determination...

78 FR 73211 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-05

... Change Relating to Multi-Class Spread Orders November 29, 2013. Pursuant to Section 19(b)(1) of the... Substance of the Proposed Rule Change CBOE proposes to amend its rule related to Multi-Class Broad-Based Index Option Spread Orders (referred to herein as ``Multi-Class Spread Orders''). The text of the...

Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans

PubMed Central

Norman, Paul J.; Hollenbach, Jill A.; Nemat-Gorgani, Neda; Guethlein, Lisbeth A.; Hilton, Hugo G.; Pando, Marcelo J.; Koram, Kwadwo A.; Riley, Eleanor M.; Abi-Rached, Laurent; Parham, Peter

2013-01-01

Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1–14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and previous associations of cerebral malaria with HLA-B*53:01 and KIR, Plasmodium falciparum is a candidate pathogen. PMID:24204327

Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid reductoisomerases.

PubMed

Cahn, Jackson K B; Brinkmann-Chen, Sabine; Spatzal, Thomas; Wiig, Jared A; Buller, Andrew R; Einsle, Oliver; Hu, Yilin; Ribbe, Markus W; Arnold, Frances H

2015-06-15

Although most sequenced members of the industrially important ketol-acid reductoisomerase (KARI) family are class I enzymes, structural studies to date have focused primarily on the class II KARIs, which arose through domain duplication. In the present study, we present five new crystal structures of class I KARIs. These include the first structure of a KARI with a six-residue β2αB (cofactor specificity determining) loop and an NADPH phosphate-binding geometry distinct from that of the seven- and 12-residue loops. We also present the first structures of naturally occurring KARIs that utilize NADH as cofactor. These results show insertions in the specificity loops that confounded previous attempts to classify them according to loop length. Lastly, we explore the conformational changes that occur in class I KARIs upon binding of cofactor and metal ions. The class I KARI structures indicate that the active sites close upon binding NAD(P)H, similar to what is observed in the class II KARIs of rice and spinach and different from the opening of the active site observed in the class II KARI of Escherichia coli. This conformational change involves a decrease in the bending of the helix that runs between the domains and a rearrangement of the nicotinamide-binding site. © The Authors Journal Compilation © 2015 Biochemical Society.

Preparation guide for class B software specification documents

NASA Technical Reports Server (NTRS)

Tausworthe, R. C.

1979-01-01

General conceptual requirements and specific application rules and procedures are provided for the production of software specification documents in conformance with deep space network software standards and class B standards. Class B documentation is identified as the appropriate level applicable to implementation, sustaining engineering, and operational uses by qualified personnel. Special characteristics of class B documents are defined.

The Chemically Inducible Plant Cytochrome P450 CYP76B1 Actively Metabolizes Phenylureas and Other Xenobiotics1

PubMed Central

Robineau, Tiburce; Batard, Yannick; Nedelkina, Svetlana; Cabello-Hurtado, Francisco; LeRet, Monique; Sorokine, Odile; Didierjean, Luc; Werck-Reichhart, Danièle

1998-01-01

Cytochrome P450s (P450s) constitute one of the major classes of enzymes that are responsible for detoxification of exogenous molecules both in animals and plants. On the basis of its inducibility by exogenous chemicals, we recently isolated a new plant P450, CYP76B1, from Jerusalem artichoke (Helianthus tuberosus) and showed that it was capable of dealkylating a model xenobiotic compound, 7-ethoxycoumarin. In the present paper we show that CYP76B1 is more strongly induced by foreign compounds than other P450s isolated from the same plant, and metabolizes with high efficiency a wide range of xenobiotics, including alkoxycoumarins, alkoxyresorufins, and several herbicides of the class of phenylureas. CYP76B1 catalyzes the double N-dealkylation of phenylureas with turnover rates comparable to those reported for physiological substrates and produces nonphytotoxic compounds. Potential uses for CYP76B1 thus include control of herbicide tolerance and selectivity, as well as soil and groundwater bioremediation. PMID:9808750

Discrete structural features among interface residue-level classes.

PubMed

Sowmya, Gopichandran; Ranganathan, Shoba

2015-01-01

Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. Our analysis showed ~60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs.

Discrete structural features among interface residue-level classes

PubMed Central

2015-01-01

Background Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. Results Our analysis showed ~60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. Conclusions Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs. PMID:26679043

Spatial clusters of daytime sleepiness and association with nighttime noise levels in a Swiss general population (GeoHypnoLaus).

PubMed

Joost, Stéphane; Haba-Rubio, José; Himsl, Rebecca; Vollenweider, Peter; Preisig, Martin; Waeber, Gérard; Marques-Vidal, Pedro; Heinzer, Raphaël; Guessous, Idris

2018-05-31

Daytime sleepiness is highly prevalent in the general adult population and has been linked to an increased risk of workplace and vehicle accidents, lower professional performance and poorer health. Despite the established relationship between noise and daytime sleepiness, little research has explored the individual-level spatial distribution of noise-related sleep disturbances. We assessed the spatial dependence of daytime sleepiness and tested whether clusters of individuals exhibiting higher daytime sleepiness were characterized by higher nocturnal noise levels than other clusters. Population-based cross-sectional study, in the city of Lausanne, Switzerland. Sleepiness was measured using the Epworth Sleepiness Scale (ESS) for 3697 georeferenced individuals from the CoLaus|PsyCoLaus cohort (period = 2009-2012). We used the sonBASE georeferenced database produced by the Swiss Federal Office for the Environment to characterize nighttime road traffic noise exposure throughout the city. We used the GeoDa software program to calculate the Getis-Ord G i * statistics for unadjusted and adjusted ESS in order to detect spatial clusters of high and low ESS values. Modeled nighttime noise exposure from road and rail traffic was compared across ESS clusters. Daytime sleepiness was not randomly distributed and showed a significant spatial dependence. The median nighttime traffic noise exposure was significantly different across the three ESS Getis cluster classes (p < 0.001). The mean nighttime noise exposure in the high ESS cluster class was 47.6, dB(A) 5.2 dB(A) higher than in low clusters (p < 0.001) and 2.1 dB(A) higher than in the neutral class (p < 0.001). These associations were independent of major potential confounders including body mass index and neighborhood income level. Clusters of higher daytime sleepiness in adults are associated with higher median nighttime noise levels. The identification of these clusters can guide tailored public health interventions. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase.

PubMed

Ruggiero, Melina; Papp-Wallace, Krisztina M; Taracila, Magdalena A; Mojica, Maria F; Bethel, Christopher R; Rudin, Susan D; Zeiser, Elise T; Gutkind, Gabriel; Bonomo, Robert A; Power, Pablo

2017-06-01

PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram-negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted omega (Ω) loop and extended B3 β-strand. These singular structural features are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i.e., k 2 / K = 2 × 10 3 ± 0.1 × 10 3 M -1 s -1 , where k 2 is the rate constant for acylation (carbamylation) and K is the equilibrium constant) that were obtained when AVI was tested were reminiscent of values observed testing the inhibition by AVI of class C and D β-lactamases (i.e., k 2 / K range of ≈10 3 M -1 s -1 ) and not class A β-lactamases (i.e., k 2 / K range, 10 4 to 10 5 M -1 s -1 ). Once AVI was bound, a stable complex with PER-2 was observed via mass spectrometry (e.g., 31,389 ± 3 atomic mass units [amu] → 31,604 ± 3 amu for 24 h). Molecular modeling of PER-2 with AVI showed that the carbonyl of AVI was located in the oxyanion hole of the β-lactamase and that the sulfate of AVI formed interactions with the β-lactam carboxylate binding site of the PER-2 β-lactamase (R220 and T237). However, hydrophobic patches near the PER-2 active site (by Ser70 and B3-B4 β-strands) were observed and may affect the binding of necessary catalytic water molecules, thus slowing acylation ( k 2 / K ) of AVI onto PER-2. Similar electrostatics and hydrophobicity of the active site were also observed between OXA-48 and PER-2, while CTX-M-15 was more hydrophilic. To demonstrate the ability of AVI to overcome the enhanced cephalosporinase activity of PER-2 β-lactamase, we tested different β-lactam-AVI combinations. By lowering MICs to ≤2 mg/liter, the ceftaroline-AVI combination could represent a favorable therapeutic option against Enterobacteriaceae expressing bla PER-2 Our studies define the inactivation of the PER-2 ESBL by AVI and suggest that the biophysical properties of the active site contribute to determining the efficiency of inactivation. Copyright © 2017 American Society for Microbiology.

Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase

PubMed Central

Ruggiero, Melina; Papp-Wallace, Krisztina M.; Taracila, Magdalena A.; Mojica, Maria F.; Bethel, Christopher R.; Rudin, Susan D.; Zeiser, Elise T.; Gutkind, Gabriel

2017-01-01

ABSTRACT PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram-negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted omega (Ω) loop and extended B3 β-strand. These singular structural features are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i.e., k2/K = 2 × 103 ± 0.1 × 103 M−1 s−1, where k2 is the rate constant for acylation (carbamylation) and K is the equilibrium constant) that were obtained when AVI was tested were reminiscent of values observed testing the inhibition by AVI of class C and D β-lactamases (i.e., k2/K range of ≈103 M−1 s−1) and not class A β-lactamases (i.e., k2/K range, 104 to 105 M−1 s−1). Once AVI was bound, a stable complex with PER-2 was observed via mass spectrometry (e.g., 31,389 ± 3 atomic mass units [amu] → 31,604 ± 3 amu for 24 h). Molecular modeling of PER-2 with AVI showed that the carbonyl of AVI was located in the oxyanion hole of the β-lactamase and that the sulfate of AVI formed interactions with the β-lactam carboxylate binding site of the PER-2 β-lactamase (R220 and T237). However, hydrophobic patches near the PER-2 active site (by Ser70 and B3-B4 β-strands) were observed and may affect the binding of necessary catalytic water molecules, thus slowing acylation (k2/K) of AVI onto PER-2. Similar electrostatics and hydrophobicity of the active site were also observed between OXA-48 and PER-2, while CTX-M-15 was more hydrophilic. To demonstrate the ability of AVI to overcome the enhanced cephalosporinase activity of PER-2 β-lactamase, we tested different β-lactam–AVI combinations. By lowering MICs to ≤2 mg/liter, the ceftaroline-AVI combination could represent a favorable therapeutic option against Enterobacteriaceae expressing blaPER-2. Our studies define the inactivation of the PER-2 ESBL by AVI and suggest that the biophysical properties of the active site contribute to determining the efficiency of inactivation. PMID:28348157

Discriminative components of data.

PubMed

Peltonen, Jaakko; Kaski, Samuel

2005-01-01

A simple probabilistic model is introduced to generalize classical linear discriminant analysis (LDA) in finding components that are informative of or relevant for data classes. The components maximize the predictability of the class distribution which is asymptotically equivalent to 1) maximizing mutual information with the classes, and 2) finding principal components in the so-called learning or Fisher metrics. The Fisher metric measures only distances that are relevant to the classes, that is, distances that cause changes in the class distribution. The components have applications in data exploration, visualization, and dimensionality reduction. In empirical experiments, the method outperformed, in addition to more classical methods, a Renyi entropy-based alternative while having essentially equivalent computational cost.

Adverse signaling of scavenger receptor class B1 and PGC1s in alcoholic hepatosteatosis and steatohepatitis and protection by betaine in rat.

PubMed

Varatharajalu, Ravi; Garige, Mamatha; Leckey, Leslie C; Arellanes-Robledo, Jaime; Reyes-Gordillo, Karina; Shah, Ruchi; Lakshman, M Raj

2014-07-01

Because scavenger receptor class B type 1 is the cholesterol uptake liver receptor, whereas peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β) and PGC-1α are critical for lipid synthesis and degradation, we investigated the roles of these signaling molecules in the actions of ethanol-polyunsaturated fatty acids and betaine on hepatosteatosis and steatohepatitis. Ethanol-polyunsaturated fatty acid treatment caused the following: i) hepatosteatosis, as evidenced by increased liver cholesterol and triglycerides, lipid score, and decreased serum adiponectin; ii) marked inhibition of scavenger receptor class B type 1 glycosylation, its plasma membrane localization, and its hepatic cholesterol uptake function; and iii) moderate steatohepatitis, as evidenced by histopathological characteristics, increased liver tumor necrosis factor α and IL-6, decreased glutathione, and elevated serum alanine aminotransferase. These actions of ethanol involved up-regulated PGC-1β, sterol regulatory element-binding proteins 1c and 2, acetyl-CoA carboxylase, and HMG-CoA reductase mRNAs/proteins and inactive non-phosphorylated AMP kinase; and down-regulated silence regulator gene 1 and PGC-1α mRNA/proteins and hepatic fatty acid oxidation. Betaine markedly blunted all these actions of ethanol on hepatosteatosis and steatohepatitis. Therefore, we conclude that ethanol-mediated impaired post-translational modification, trafficking, and function of scavenger receptor class B type 1 may account for alcoholic hyperlipidemia. Up-regulation of PGC-1β and lipid synthetic genes and down-regulation of silence regulator gene 1, PGC-1α, adiponectin, and lipid degradation genes account for alcoholic hepatosteatosis. Induction of proinflammatory cytokines and depletion of endogenous antioxidant, glutathione, account for alcoholic steatohepatitis. We suggest betaine as a potential therapeutic agent because it effectively protects against adverse actions of ethanol. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Coevolution of the ATPase ClpV, the Sheath Proteins TssB and TssC, and the Accessory Protein TagJ/HsiE1 Distinguishes Type VI Secretion Classes*

PubMed Central

Förster, Andreas; Planamente, Sara; Manoli, Eleni; Lossi, Nadine S.; Freemont, Paul S.; Filloux, Alain

2014-01-01

The type VI secretion system (T6SS) is a bacterial nanomachine for the transport of effector molecules into prokaryotic and eukaryotic cells. It involves the assembly of a tubular structure composed of TssB and TssC that is similar to the tail sheath of bacteriophages. The sheath contracts to provide the energy needed for effector delivery. The AAA+ ATPase ClpV disassembles the contracted sheath, which resets the systems for reassembly of an extended sheath that is ready to fire again. This mechanism is crucial for T6SS function. In Vibrio cholerae, ClpV binds the N terminus of TssC within a hydrophobic groove. In this study, we resolved the crystal structure of the N-terminal domain of Pseudomonas aeruginosa ClpV1 and observed structural alterations in the hydrophobic groove. The modification in the ClpV1 groove is matched by a change in the N terminus of TssC, suggesting the existence of distinct T6SS classes. An accessory T6SS component, TagJ/HsiE, exists predominantly in one of the classes. Using bacterial two-hybrid approaches, we showed that the P. aeruginosa homolog HsiE1 interacts strongly with ClpV1. We then resolved the crystal structure of HsiE1 in complex with the N terminus of HsiB1, a TssB homolog and component of the contractile sheath. Phylogenetic analysis confirmed that these differences distinguish T6SS classes that resulted from a functional co-evolution between TssB, TssC, TagJ/HsiE, and ClpV. The interaction of TagJ/HsiE with the sheath as well as with ClpV suggests an alternative mode of disassembly in which HsiE recruits the ATPase to the sheath. PMID:25305017

Avibactam and Inhibitor-Resistant SHV β-Lactamases

PubMed Central

Winkler, Marisa L.; Papp-Wallace, Krisztina M.; Taracila, Magdalena A.

2015-01-01

β-Lactamase enzymes (EC 3.5.2.6) are a significant threat to the continued use of β-lactam antibiotics to treat infections. A novel non-β-lactam β-lactamase inhibitor with activity against many class A and C and some class D β-lactamase variants, avibactam, is now available in the clinic in partnership with ceftazidime. Here, we explored the activity of avibactam against a variety of characterized isogenic laboratory constructs of β-lactamase inhibitor-resistant variants of the class A enzyme SHV (M69I/L/V, S130G, K234R, R244S, and N276D). We discovered that the S130G variant of SHV-1 shows the most significant resistance to inhibition by avibactam, based on both microbiological and biochemical characterizations. Using a constant concentration of 4 mg/liter of avibactam as a β-lactamase inhibitor in combination with ampicillin, the MIC increased from 1 mg/liter for blaSHV-1 to 256 mg/liter for blaSHV S130G expressed in Escherichia coli DH10B. At steady state, the k2/K value of the S130G variant when inactivated by avibactam was 1.3 M−1 s−1, versus 60,300 M−1 s−1 for the SHV-1 β-lactamase. Under timed inactivation conditions, we found that an approximately 1,700-fold-higher avibactam concentration was required to inhibit SHV S130G than the concentration that inhibited SHV-1. Molecular modeling suggested that the positioning of amino acids in the active site of SHV may result in an alternative pathway of inactivation when complexed with avibactam, compared to the structure of CTX-M-15–avibactam, and that S130 plays a role in the acylation of avibactam as a general acid/base. In addition, S130 may play a role in recyclization. As a result, we advance that the lack of a hydroxyl group at position 130 in the S130G variant of SHV-1 substantially slows carbamylation of the β-lactamase by avibactam by (i) removing an important proton acceptor and donator in catalysis and (ii) decreasing the number of H bonds. In addition, recyclization is most likely also slow due to the lack of a general base to initiate the process. Considering other inhibitor-resistant mechanisms among class A β-lactamases, S130 may be the most important amino acid for the inhibition of class A β-lactamases, perhaps even for the novel diazabicyclooctane class of β-lactamase inhibitors. PMID:25691639

Model uncertainties of the 2002 update of California seismic hazard maps

USGS Publications Warehouse

Cao, T.; Petersen, M.D.; Frankel, A.D.

2005-01-01

In this article we present and explore the source and ground-motion model uncertainty and parametric sensitivity for the 2002 update of the California probabilistic seismic hazard maps. Our approach is to implement a Monte Carlo simulation that allows for independent sampling from fault to fault in each simulation. The source-distance dependent characteristics of the uncertainty maps of seismic hazard are explained by the fundamental uncertainty patterns from four basic test cases, in which the uncertainties from one-fault and two-fault systems are studied in detail. The California coefficient of variation (COV, ratio of the standard deviation to the mean) map for peak ground acceleration (10% of exceedance in 50 years) shows lower values (0.1-0.15) along the San Andreas fault system and other class A faults than along class B faults (0.2-0.3). High COV values (0.4-0.6) are found around the Garlock, Anacapa-Dume, and Palos Verdes faults in southern California and around the Maacama fault and Cascadia subduction zone in northern California.

46 CFR 108.173 - Class I, Division 2 locations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... locations. The following are Class I, Division 2 locations: (a) An enclosed space that has any open portion... mud pit. (b) A location in the weather that is— (1) Within the boundaries of the drilling derrick up...

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidate Andrew Morgan looks over work platforms to gain a look at the Orion spacecraft being prepared for Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett Selected image has been cropped

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidate Josh Cassada looks over work platforms to gain a look at the Orion spacecraft being prepared for Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidates Tyler Nick Hague, left, Christina Hammock, center, and Victor Glover listen to a briefing on preparations for the launch the Orion spacecraft on Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidates Jessica Meir, left, Andrew Morgan, center, and Anne McClain listen to a briefing on preparations for the launch the Orion spacecraft on Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidate Victor Glover looks over work platforms to gain a look at the Orion spacecraft being prepared for Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidate Tyler Nick Hague examines part of the thermal protection system for the agency's Orion spacecraft being prepared for Exploration Flight Test, or EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, associate center director Kelvin Manning, left, briefs astronaut candidates Nicole Mann, center, and Tyler Nick Hague on preparations for the launch the Orion spacecraft on Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

Hanford Site Asbestos Abatement Plan. Revision 1

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

Mewes, B.S.

The Hanford Site Asbestos Abatement Plan (Plan) lists priorities for asbestos abatement activities to be conducted in Hanford Site facilities. The Plan is based on asbestos assessment information gathered in fiscal year 1989 that evaluated all Hanford Site facilities for the presence and condition of asbestos. Of those facilities evaluated, 414 contain asbestos-containing materials and are classified according to the potential risk of asbestos exposure to building personnel. The Plan requires that asbestos condition update reports be prepared for all affected facilities. The reporting is completed by the asbestos coordinator for each of the 414 affected facilities and transmitted tomore » the Plan manager annually. The Plan manager uses this information to reprioritize future project lists. Currently, five facilities are determined to be Class Al, indicating a high potential for asbestos exposure. Class Al and B1 facilities are the highest priority for asbestos abatement. Abatement of the Class A1 and Bl facilities is scheduled through fiscal year 1997. Removal of asbestos in B1 facilities will reduce the risk for further Class ``A`` conditions to arise.« less

A Latent Class Analysis of Adolescent Gambling: Application of Resilience Theory

ERIC Educational Resources Information Center

Goldstein, Abby L.; Faulkner, Breanne; Cunningham, Rebecca M.; Zimmerman, Marc A.; Chermack, Stephen; Walton, Maureen A.

2013-01-01

The current study examined the application of resilience theory to adolescent gambling using Latent Class Analysis (LCA) to establish subtypes of adolescent gamblers and to explore risk and promotive factors associated with gambling group membership. Participants were a diverse sample of 249 adolescents ages 14 to 18 (30.1 % female, 59.4 % African…

Polydrug use typologies and childhood maltreatment in a nationally representative survey of Danish young adults.

PubMed

Armour, Cherie; Shorter, Gillian W; Elhai, Jon D; Elklit, Ask; Christoffersen, Mogens N

2014-01-01

Substance use and childhood maltreatment experience are linked, but little is known about the association with polydrug use patterns. Latent class analyses (LCA) were performed on eight illicit drugs in a random population sample of young Danes separated by sex (males: n = 1,555; females: n = 1,425). Logistic regressions explored associations of polydrug use patterns and childhood maltreatment. A three-class solution best described patterns of polydrug use in both the male and female samples. Across all LCA models, Class 1 was characterized by individuals who represented wide-range polydrug users, endorsing many of the drug types (males = 8%; females = 2%). Class 2 was characterized by amphetamine, cannabis, cocaine, and amyl nitrate users (males = 18%; females = 7%). Class 3 was characterized by individuals who endorsed either low-level use of cannabis only or no drug use (males = 74%; females = 91 %). For males, having been a child-protection case was associated with Classes 1 and 2 and for females with Class 2, compared with Class 3. Alcohol problems were associated with Classes 1 and 2 for both sexes. Sexual abuse was associated with Classes 1 and 2 for females but not males, whereas physical abuse was associated with Classes 1 and 2 for males but not females, as compared with Class 3. Separate sex analyses are important; although patterns of polydrug use are broadly similar, females are less frequently polydrug users. In addition, different relationships exist for the sexes, such that polydrug use patterns are associated with sexual abuse in females, whereas such patterns are associated with physical abuse in young males.

Children's responses to mother-infant and father-infant interaction with a baby sibling: jealousy or joy?

PubMed

Volling, Brenda L; Yu, Tianyi; Gonzalez, Richard; Kennedy, Denise E; Rosenberg, Lauren; Oh, Wonjung

2014-10-01

Firstborn children's reactions to mother-infant and father-infant interaction after a sibling's birth were examined in an investigation of 224 families. Triadic observations of parent-infant-sibling interaction were conducted at 1 month after the birth. Parents reported on children's problem behaviors at 1 and 4 months after the birth and completed the Attachment Q-sort before the birth. Latent profile analysis (LPA) identified 4 latent classes (behavioral profiles) for mother-infant and father-infant interactions: regulated-exploration, disruptive-dysregulated, approach-avoidant, and anxious-clingy. A fifth class, attention-seeking, was found with fathers. The regulated-exploration class was the normative pattern (60%), with few children in the disruptive class (2.7%). Approach-avoidant children had more behavior problems at 4 months than any other class, with the exception of the disruptive children, who were higher on aggression and attention problems. Before the birth, anxious-clingy children had less secure attachments to their fathers than approach avoidant children but more secure attachments to their mothers. Results underscore individual differences in firstborns' behavioral responses to parent-infant interaction and the importance of a person-centered approach for understanding children's jealousy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Stripped Red Giants - Helium Core White Dwarf Progenitors and their sdB Siblings

NASA Astrophysics Data System (ADS)

Heber, U.

2017-03-01

Some gaps in the mosaic of binary star evolution have recently been filled by the discoveries of helium-core white dwarf progenitors (often called extremely low mass (ELM) white dwarfs) as stripped cores of first-giant branch objects. Two varieties can be distinguished. One class is made up by SB1 binaries, companions being white dwarfs as well. Another class, the so-called EL CVn stars, are composite spectrum binaries, with A-Type companions. Pulsating stars are found among both classes. A riddle is posed by the apparently single objects. There is a one-to-one correspondence of the phenomena found for these new classes of star to those observed for sdB stars. In fact, standard evolutionary scenarios explain the origin of sdB stars as red giants that have been stripped close to the tip of first red giant branch. A subgroup of subluminous B stars can also be identified as stripped helium-cores of red giants. They form an extension of the ELM sequence to higher temperatures. Hence low mass white dwarfs of helium cores and sdB stars in binaries are close relatives in terms of stellar evolution.

Class Explorations in Space: From the Blackboard and History to the Outdoors and Future

NASA Astrophysics Data System (ADS)

Cavicchi, Elizabeth

2011-11-01

Our everyday activities occur so seamlessly in the space around us as to leave us unawares of space, its properties, and our use of it. What might we notice, wonder about and learn through interacting with space exploratively? My seminar class took on that question as an opening for personal and group experiences during this semester. In the process, they observe space locally and in the sky, read historical works of science involving space, and invent and construct forms in space. All these actions arise responsively, as we respond to: physical materials and space; historical resources; our seminar participants, and future learners. Checks, revisions and further developments -- on our findings, geometrical constructions, shared or personal inferences---come about observationally and collaboratively. I teach this seminar as an expression of the research pedagogy of critical exploration, developed by Eleanor Duckworth from the work of Jean Piaget, B"arbel Inhelder and the Elementary Science Study. This practice applies the quest for understanding of a researcher to spontaneous interactions evolving within a classroom. The teacher supports students in satisfying and developing their curiosities, which often results in exploring the subject matter by routes that are novel to both teacher and student. As my students ``mess about'' with geometry, string and chalk at the blackboard, in their notebooks, and in response to propositions in Euclid's Elements, they continually imagine further novel venues for using geometry to explore space. Where might their explorations go in the future? I invite you to hear from them directly!

Increased seroprevalence of IgG-class antibodies against cytomegalovirus, parvovirus B19, and varicella-zoster virus in women working in child day care

PubMed Central

2012-01-01

Background Primary maternal infection with cytomegalovirus (CMV), parvovirus B19 (B19V), and varicella-zoster virus (VZV) may result in adverse pregnancy outcomes like congenital infection or foetal loss. Women working in child day care have an increased exposure to CMV, B19V, and VZV. By comparing the seroprevalence of IgG-class antibodies against CMV, VZV and B19V in female day care workers (DCW) with the seroprevalence in women not working in day care this study aimed to assess the association between occupation and infection. Methods A cross-sectional design was used. Out of a random sample of 266 day care centres, demographic data, data on work history, and blood samples were collected from 285 women from 38 centres. In addition, blood samples and basic demographics from women who participated in a cross-sectional survey of the Amsterdam population (2004) were used. All blood samples were tested for IgG-class antibodies against CMV, B19V, and VZV. Results Twenty-seven percent of the DCW were still susceptible to B19V or CMV. Working in day care was independently associated with B19V infection in all DCW (prevalence ratio [PR] 1.2; 95 % CI 1.1–1.3), and with CMV infection in DCW of European origin only (PR 1.7; 95 % CI 1.3–2.3). Almost all women born outside Europe tested seropositive for CMV (96 %). All DCW tested seropositive for VZV, compared to only 94 % of the women not working in day care. Conclusion This study confirms the clear association between employment in child day care centres and infection with CMV and B19V. Intervention policies, like screening of new employees and awareness campaigns emphasizing hygienic measures among DCW, should be implemented urgently to improve the maternal health of these women and the health of their offspring. PMID:22726391

B and T Cell Epitope-Based Peptides Predicted from Evolutionarily Conserved and Whole Protein Sequences of Ebola Virus as Vaccine Targets.

PubMed

Yasmin, T; Nabi, A H M Nurun

2016-05-01

Ebola virus (EBV) has become a serious threat to public health. Different approaches were applied to predict continuous and discontinuous B cell epitopes as well as T cell epitopes from the sequence-based and available three-dimensional structural analyses of each protein of EBV. Peptides '(79) VPSATKRWGFRSGVPP(94) ' from GP1 and '(515) LHYWTTQDEGAAIGLA(530) ' from GP2 of Ebola were found to be the consensus peptidic sequences predicted as linear B cell epitope of which the latter contains a region (519) TTQDEG(524) that fulfilled all the criteria of accessibility, hydrophilicity, flexibility and beta turn region for becoming an ideal B cell epitope. Different nonamers as T cell epitopes were obtained that interacted with different numbers of MHC class I and class II alleles with a binding affinity of <100 nm. Interestingly, these alleles also bound to the MHC class I alleles mostly prevalent in African and South Asian regions. Of these, 'LANETTQAL' and 'FLYDRLAST' nonamers were predicted to be the most potent T cell epitopes and they, respectively, interacted with eight and twelve class I alleles that covered 63.79% and 54.16% of world population, respectively. These nonamers were found to be the core sequences of 15mer peptides that interacted with the most common class II allele, HLA-DRB1*01:01. They were further validated for their binding to specific class I alleles using docking technique. Thus, these predicted epitopes may be used as vaccine targets against EBV and can be validated in model hosts to verify their efficacy as vaccine. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Purification and characterization of a rice class I chitinase, OsChia1b, produced in Esherichia coli.

PubMed

Mizuno, Ryoji; Itoh, Yoshikane; Nishizawa, Yoko; Kezuka, Yuichiro; Suzuki, Kazushi; Nonaka, Takamasa; Watanabe, Takeshi

2008-03-01

To determine the properties and structure of OsChia1b, a family 19 chitinase from Oryza sativa L. cv. Nipponbare (japonica ssp.), recombinant OsChia1b was produced in Esherichia coli cells and purified to homogeneity by chitin affinity column chromatography. OsChia1b was highly active against soluble chitinous substrate, but not against crystalline chitin, and clearly inhibited hyphal extension of Trichoderma reesei.

75 FR 14225 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-24

... Rule Change To Permit Concurrent Listing of $3.50 and $4 Strikes for Classes in the $0.50 Strike and $1... ``Act''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 10, 2010, the... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. \\3\\ 15 U.S.C. 78s(b)(3)(A). \\4\\ 17 CFR 240...

47 CFR 36.372 - Marketing-Account 6610 (Class B telephone companies); Accounts 6611 and 6613 (Class A telephone...

Code of Federal Regulations, 2011 CFR

2011-10-01

... analysis of current billing for a representative period, excluding current billing on behalf of others and billing in connection with intercompany setttlements. Effective July 1, 2001 through June 30, 2012, all...

47 CFR 36.372 - Marketing-Account 6610 (Class B telephone companies); Accounts 6611 and 6613 (Class A telephone...

Code of Federal Regulations, 2010 CFR

2010-10-01

... analysis of current billing for a representative period, excluding current billing on behalf of others and billing in connection with intercompany setttlements. Effective July 1, 2001 through June 30, 2011, all...

48 CFR 2901.404 - Class deviations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... through the Director, DAMS. (b) Requests for deviations under paragraph (a) of this section must be... contracting actions which will be affected. (c) For a FAR class deviation the Director, DAMS will consult with... Director, DAMS as required in FAR 1.404. ...

48 CFR 2901.404 - Class deviations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... through the Director, DAMS. (b) Requests for deviations under paragraph (a) of this section must be... contracting actions which will be affected. (c) For a FAR class deviation the Director, DAMS will consult with... Director, DAMS as required in FAR 1.404. ...

Do physical abuse, depression, and parental substance use influence patterns of substance use among child welfare involved youth? Substance use misuse.

PubMed

Snyder, Susan M; Smith, Rachel E

2015-01-01

To date studies have not explored patterns of substance use exclusively among youth in the child welfare system. Consequently, little is known about polysubstance use among child welfare-involved youth. This study aimed to explore whether physical abuse, parental substance use, depression, and demographic characteristics predict distinct patterns of substance use among child welfare-involved youth using latent class analysis (LCA). The sample included 822 11-17 year olds who participated in the National Survey of Child and Adolescent Well-being (NSCAW II) study between March 2008 and September 2009. We found the following three classes: (1) polysubstance use, (2) alcohol and marijuana use, and (3) low use. Older youth and youth who experienced physical abuse were at greater risk of being in the polysubstance use class, while living with a biological parent reduced the likelihood of polysubstance use class membership. Youth in the alcohol and marijuana use class were more likely to be older and depressed. Results from this study illuminate important targets for interventions.

Genome-Wide Identification of TCP Family Transcription Factors in Medicago truncatula Reveals Significant Roles of miR319-Targeted TCPs in Nodule Development

PubMed Central

Wang, Hongfeng; Wang, Hongwei; Liu, Rong; Xu, Yiteng; Lu, Zhichao; Zhou, Chuanen

2018-01-01

TCP proteins, the plant-specific transcription factors, are involved in the regulation of multiple aspects of plant development among different species, such as leaf development, branching, and flower symmetry. However, thus far, the roles of TCPs in legume, especially in nodulation are still not clear. In this study, a genome-wide analysis of TCP genes was carried out to discover their evolution and function in Medicago truncatula. In total, 21 MtTCPs were identified and classified into class I and class II, and the class II MtTCPs were further divided into two subclasses, CIN and CYC/TB1. The expression profiles of MtTCPs are dramatically different. The universal expression of class I MtTCPs was detected in all organs. However, the MtTCPs in CIN subclass were highly expressed in leaf and most of the members in CYC/TB1 subclass were highly expressed in flower. Such organ-specific expression patterns of MtTCPs suggest their different roles in plant development. In addition, most MtTCPs were down-regulated during the nodule development, except for the putative MtmiR319 targets, MtTCP3, MtTCP4, and MtTCP10A. Overexpression of MtmiR319A significantly reduced the expression level of MtTCP3/4/10A/10B and resulted in the decreased nodule number, indicating the important roles of MtmiR319-targeted MtTCPs in nodulation. Taken together, this study systematically analyzes the MtTCP gene family at a genome-wide level and their possible functions in nodulation, which lay the basis for further explorations of MtmiR319/MtTCPs module in association with nodule development in M. truncatula.

Wealth and the inflated self: class, entitlement, and narcissism.

PubMed

Piff, Paul K

2014-01-01

Americans may be more narcissistic now than ever, but narcissism is not evenly distributed across social strata. Five studies demonstrated that higher social class is associated with increased entitlement and narcissism. Upper-class individuals reported greater psychological entitlement (Studies 1a, 1b, and 2) and narcissistic personality tendencies (Study 2), and they were more likely to behave in a narcissistic fashion by opting to look at themselves in a mirror (Study 3). Finally, inducing egalitarian values in upper-class participants decreased their narcissism to a level on par with their lower-class peers (Study 4). These findings offer novel evidence regarding the influence of social class on the self and highlight the importance of social stratification to understanding basic psychological processes.

Secondary science students' beliefs about class discussions: a case study comparing and contrasting academic tracks

NASA Astrophysics Data System (ADS)

Silva Pimentel, Diane; McNeill, Katherine L.

2016-08-01

The dialogue that occurs in science classrooms has been the subject of research for many decades. Most studies have focused on the actual discourse that occurs and the role of the teacher in guiding the discourse. This case study explored the neglected perspective of secondary science students and their beliefs about their role in class discussions. The study participants (N = 45) were students in one of the three differentially tracked chemistry classes taught by the same teacher. Findings about the differences that exist among students from different academic tracks are reported. While it seems that epistemological beliefs focusing on content are common for the students in this study, the students' social framing in the different tracks is important to consider when teachers attempt to transition to more dialogic forms of discourse. Some key findings of this study are (a) students' beliefs that science is a body of facts to be learned influenced the factors they deemed important for whole-class discussion, (b) students from the lower-level track who typically were associated with lower socioeconomic status were more likely to view their role as passive, and (c) students' comfort level with the members of the class seemed to influence their decisions to participate in class discussions.

Isolation and characterization of major histocompatibility complex class II B genes in cranes.

PubMed

Kohyama, Tetsuo I; Akiyama, Takuya; Nishida, Chizuko; Takami, Kazutoshi; Onuma, Manabu; Momose, Kunikazu; Masuda, Ryuichi

2015-11-01

In this study, we isolated and characterized the major histocompatibility complex (MHC) class II B genes in cranes. Genomic sequences spanning exons 1 to 4 were amplified and determined in 13 crane species and three other species closely related to cranes. In all, 55 unique sequences were identified, and at least two polymorphic MHC class II B loci were found in most species. An analysis of sequence polymorphisms showed the signature of positive selection and recombination. A phylogenetic reconstruction based on exon 2 sequences indicated that trans-species polymorphism has persisted for at least 10 million years, whereas phylogenetic analyses of the sequences flanking exon 2 revealed a pattern of concerted evolution. These results suggest that both balancing selection and recombination play important roles in the crane MHC evolution.

Can Single-Sex Classes in Co-Educational Schools Enhance the Learning Experiences of Girls and/or Boys? An Exploration of Pupils' Perceptions.

ERIC Educational Resources Information Center

Jackson, Carolyn

2002-01-01

Explores the value of introducing single-sex classes within co-educational schools. Draws upon perspectives of girls and boys involved in one such initiative. Concludes girls-only classes may have positive effects for girls, but curriculum-as-usual boys' classes do nothing to challenge problematic male cultures inherent in schools. (BT)

HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.

PubMed

Stephens, Camilla; López-Nevot, Miguel-Ángel; Ruiz-Cabello, Francisco; Ulzurrun, Eugenia; Soriano, Germán; Romero-Gómez, Manuel; Moreno-Casares, Antonia; Lucena, M Isabel; Andrade, Raúl J

2013-01-01

The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases. High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls. The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07). HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.

HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity

PubMed Central

Stephens, Camilla; López-Nevot, Miguel-Ángel; Ruiz-Cabello, Francisco; Ulzurrun, Eugenia; Soriano, Germán; Romero-Gómez, Manuel; Moreno-Casares, Antonia; Lucena, M. Isabel; Andrade, Raúl J.

2013-01-01

Background and Aim The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases. Methods High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls. Results The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy’s Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07). Conclusions HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. PMID:23874514

The Ia.2 Epitope Defines a Subset of Lipid Raft Resident MHC Class II Molecules Crucial to Effective Antigen Presentation1

PubMed Central

Busman-Sahay, Kathleen; Sargent, Elizabeth; Harton, Jonathan A.; Drake, James R.

2016-01-01

Previous work has established that binding of the 11-5.2 anti-I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-Ak mAb that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2 bearing subset of I-Ak class II molecules is critically necessary for effective B cell–T cell interactions especially at low antigen doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-Ak class II molecules possessing a β chain-tethered HEL peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2 negative tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous antigen to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II confomer vital to the initiation of MHC class II restricted B cell–T cell interactions. PMID:21543648

Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

PubMed Central

Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

2014-01-01

Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer.

PubMed

Guo, Erna; Wei, Haotang; Liao, Xiwen; Xu, Yang; Li, Shu; Zeng, Xiaoyun

2018-04-01

Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses. Hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the relative risk of GC survival. Overall, 593 patients with GC and 7 ADH genes were included in the survival analysis. High expression of ADH 1A (class 1), α polypeptide ( ADH1A; log-rank P=0.043; HR=0.79; 95% CI: 0.64-0.99), ADH 1B (class 1), β polypeptide ( ADH1B ; log-rank P=1.9×10 -05 ; HR=0.65; 95% CI: 0.53-0.79) and ADH 5 (class III), χ polypeptide ( ADH5 ; log-rank P=0.0011; HR=0.73; 95% CI: 0.6-0.88) resulted in a significantly decreased risk of mortality in all patients with GC compared with patients with low expression of those genes. Furthermore, protective effects may additionally be observed in patients with intestinal-type GC with high expression of ADH1B (log-rank P=0.031; HR=0.64; 95% CI: 0.43-0.96) and patients with diffuse-type GC with high expression of ADH1A (log-rank P=0.014; HR=0.51; 95% CI: 0.3-0.88), ADH1B (log-rank P=0.04; HR=0.53; 95% CI: 0.29-0.98), ADH 4 (class II), π polypeptide (log-rank P=0.033; HR=0.58; 95% CI: 0.35-0.96) and ADH 6 (class V) (log-rank P=0.037; HR=0.59; 95% CI: 0.35-0.97) resulting in a significantly decreased risk of mortality compared with patients with low expression of those genes. In contrast, patients with diffuse-type GC with high expression of ADH5 (log-rank P=0.044; HR=1.66; 95% CI: 1.01-2.74) were significantly correlated with a poor prognosis. The results of the present study suggest that ADH1A and ADH1B may be potential prognostic biomarkers of GC, whereas the prognostic value of other ADH genes requires further investigation.

Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer

PubMed Central

Guo, Erna; Wei, Haotang; Liao, Xiwen; Xu, Yang; Li, Shu; Zeng, Xiaoyun

2018-01-01

Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses. Hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the relative risk of GC survival. Overall, 593 patients with GC and 7 ADH genes were included in the survival analysis. High expression of ADH 1A (class 1), α polypeptide (ADH1A; log-rank P=0.043; HR=0.79; 95% CI: 0.64–0.99), ADH 1B (class 1), β polypeptide (ADH1B; log-rank P=1.9×10−05; HR=0.65; 95% CI: 0.53–0.79) and ADH 5 (class III), χ polypeptide (ADH5; log-rank P=0.0011; HR=0.73; 95% CI: 0.6–0.88) resulted in a significantly decreased risk of mortality in all patients with GC compared with patients with low expression of those genes. Furthermore, protective effects may additionally be observed in patients with intestinal-type GC with high expression of ADH1B (log-rank P=0.031; HR=0.64; 95% CI: 0.43–0.96) and patients with diffuse-type GC with high expression of ADH1A (log-rank P=0.014; HR=0.51; 95% CI: 0.3–0.88), ADH1B (log-rank P=0.04; HR=0.53; 95% CI: 0.29–0.98), ADH 4 (class II), π polypeptide (log-rank P=0.033; HR=0.58; 95% CI: 0.35–0.96) and ADH 6 (class V) (log-rank P=0.037; HR=0.59; 95% CI: 0.35–0.97) resulting in a significantly decreased risk of mortality compared with patients with low expression of those genes. In contrast, patients with diffuse-type GC with high expression of ADH5 (log-rank P=0.044; HR=1.66; 95% CI: 1.01–2.74) were significantly correlated with a poor prognosis. The results of the present study suggest that ADH1A and ADH1B may be potential prognostic biomarkers of GC, whereas the prognostic value of other ADH genes requires further investigation. PMID:29552190

VizieR Online Data Catalog: Reference Catalogue of Bright Galaxies (RC1; de Vaucouleurs+ 1964)

NASA Astrophysics Data System (ADS)

de Vaucouleurs, G.; de Vaucouleurs, A.

1995-11-01

The Reference Catalogue of Bright Galaxies lists for each entry the following information: NGC number, IC number, or A number; A, B, or C designation; B1950.0 positions, position at 100 year precession; galactic and supergalactic positions; revised morphological type and source; type and color class in Yerkes list 1 and 2; Hubble-Sandage type; revised Hubble type according to Holmberg; logarithm of mean major diameter (log D) and ratio of major to minor diameter (log R) and their weights; logarithm of major diameter; sources of the diameters; David Dunlap Observatory type and luminosity class; Harvard photographic apparent magnitude; weight of V, B-V(0), U-B(0); integrated magnitude B(0) and its weight in the B system; mean surface brightness in magnitude per square minute of arc and sources for the B magnitude; mean B surface brightness derived from corrected Harvard magnitude; the integrated color index in the standard B-V system; "intrinsic" color index; sources of B-V and/or U-B; integrated color in the standard U-B system; observed radial velocity in km/sec; radial velocity corrected for solar motion in km/sec; sources of radial velocities; solar motion correction; and direct photographic source. The catalog was created by concatenating four files side by side. (1 data file).

[Non-pharmacologic therapy of hypertrophic obstructive cardiomyopathy--results of therapy based on percutaneous transluminal septal myocardial ablation compared with results of dual-chamber cardiac pacing].

PubMed

Krejcí, J; Groch, L; Meluzín, J; Vykypel, T; Halámek, J; Vitovec, J

2006-04-01

Percutaneous transluminal septal myocardial ablation (PTSMA) and pacemaker (PM) therapy with apical preexcitation are therapeutic options for hypertrophic obstructive cardiomyopathy (HOCM) patients with symptoms despite pharmacological therapy. evaluation and comparison of treatment results of PTSMA and PM implantation. 22 HOCM patients (NYHA class III and IV) with left ventricle outflow tract gradient (LVOTG) at rest more than 30 mm Hg. In group A were evaluated 11 patients treated by PTSMA. Left ventricle outflow tract gradient (LVOTG) was 90.5 +/- 16.0 mm Hg, NYHA class 3.1 +/- 0.2. Group B included 11 patients treated by dual chamber PM implantation, LVOTG in this group was 105 +/- 48 mm Hg, NYHA class 3.0 +/- 0.4. NYHA class in the group A decreased after treatment to 1.8 +/- 0.6 (p < 0.01), LVOTG to 24 +/- 12 mm Hg (p < 0.001). There was observed significant decrease in grade of systolic anterior motion (SAM), interventricular septum (IVS) thickness and left atrium (LA) size. Left ventricle end systolic diameter (LV SD) and left ventricle end diastolic diameter (LV DD) increased during follow-up. Decrease of NYHA class in the group B was to 2.1 +/- 0.6 (p < 0.001), LVOTG to 25.5 +/- 21.0 mm Hg (p < 0.001). Changes of other parameters in the group B were not significant, except decrease of SAM. Comparison of both groups: NYHA class change PTSMA/PM: 1.3 +/- 0.6/0.9 +/- 0.4 (p < 0.05), LVOTG change PTSMA/PM: -66 +/- 20/-79 +/- 46 mm Hg (p = n.s.). LV SD assessment comparison of LV SD change PTSMA/PM: 5 +/- 5/1 +/- 5 mm (p < 0.05). LA assessment - comparison of LA change PTSMA/PM: 5 +/- 5/-1 +/- 4 mm (p < 0.05). Other changes were not significant. Both therapeutic approaches - PTSMA and PM implantation - resulted in significant improvement of functional capacity assessed by NYHA classification. Decrease of LVOTG was also significant and was similar in both groups, NYHA class improvement as well as LA size decrease and LV DS increase were more expressed in PTSMA group.

Dynamic analysis of a hepatitis B model with three-age-classes

NASA Astrophysics Data System (ADS)

Zhang, Suxia; Zhou, Yicang

2014-07-01

Based on the fact that the likelihood of becoming chronically infected is dependent on age at primary infection Kane (1995) [2], Edmunds et al. (1993) [3], Medley et al. (2001) [4], and Ganem and Prince (2004) [6], we formulate a hepatitis B transmission model with three age classes. The reproduction number, R0 is defined and the dynamical behavior of the model is analyzed. It is proved that the disease-free equilibrium is globally stable if R0<1, and there exists at least one endemic equilibrium and that the disease is uniformly persistent if R0>1. The unique endemic equilibrium and its global stability is obtained in a special case. Simulations are also conducted to compare the dynamical behavior of the model with and without age classes.

Oxidative bioactivation of abacavir in subcellular fractions of human antigen presenting cells.

PubMed

Bell, Catherine C; Santoyo Castelazo, Anahi; Yang, Emma L; Maggs, James L; Jenkins, Rosalind E; Tugwood, Jonathan; O'Neill, Paul M; Naisbitt, Dean J; Park, B Kevin

2013-07-15

Human exposure to abacavir, a primary alcohol antiretroviral, is associated with the development of immunological drug reactions in individuals carrying the HLA risk allele B*57:01. Interaction of abacavir with antigen presenting cells results in cell activation through an Hsp70-mediated Toll-like receptor pathway and the provision of T-cell antigenic determinants. Abacavir's electrophilic aldehyde metabolites are potential precursors of neoantigens. Herein, we have used mass spectrometry to study the oxidative metabolism of abacavir in EBV-transformed human B-cells. RNA and protein were isolated from the cells and subjected to transcriptomic and mass spectrometric analyses to identify the redox enzymes expressed. Low levels of isomeric abacavir carboxylic acids were detected in subcellular fractions of EBV-transformed human B-cells incubated with abacavir. Metabolite formation was time-dependent but was not reduced by an inhibitor of Class I alcohol dehydrogenases. Relatively high levels of mRNA were detected for several redox enzymes, including alcohol dehydrogenase 5 (Class III), aldehyde dehydrogenases (ALDH3A2, ALDH6A1, and ALDH9A1), CYP1B1, CYP2R1, CYP7B1, and hydroxysteroid dehydrogenase 10. Over 2600 proteins were identified by mass spectrometry. More than 1000 of these proteins exhibited catalytic activity, and 80 were oxido-reductases. This is the first proteomic inventory of enzymes in antigen presenting cells. However, neither of the hepatic alcohol dehydrogenases of Class I which metabolize abacavir in vitro was expressed at the protein level. Nevertheless the metabolic production of abacavir carboxylic acids by B-cell fractions implies abacavir-treated immune cells might be exposed to the drug's protein-reactive aldehyde metabolites in vivo.

The Effects of Differential Training Procedures on Linked Perceptual Class Formation

ERIC Educational Resources Information Center

Fields, Lanny; Tittelbach, Danielle; Shamoun, Kimberly; Watanabe, Mari; Fitzer, Adrienne; Matneja, Priya

2007-01-01

When the stimuli in one perceptual class (A') become related to the stimuli in another perceptual class (B'), the two are functioning as a single "linked perceptual class". A common linked perceptual class would be the sounds of a person's voice (class A') and the pictures of that person (class B'). Such classes are ubiquitous in real…

Structure of the full-length glucagon class B G protein-coupled receptor

PubMed Central

Zhang, Haonan; Qiao, Anna; Yang, Dehua; Yang, Linlin; Dai, Antao; de Graaf, Chris; Reedtz-Runge, Steffen; Dharmarajan, Venkatasubramanian; Zhang, Hui; Han, Gye Won; Grant, Thomas D.; Sierra, Raymond G.; Weierstall, Uwe; Nelson, Garrett; Liu, Wei; Wu, Yanhong; Ma, Limin; Cai, Xiaoqing; Lin, Guangyao; Wu, Xiaoai; Geng, Zhi; Dong, Yuhui; Song, Gaojie; Griffin, Patrick R.; Lau, Jesper; Cherezov, Vadim; Yang, Huaiyu; Hanson, Michael A.; Stevens, Raymond C.; Zhao, Qiang; Jiang, Hualiang; Wang, Ming-Wei; Wu, Beili

2017-01-01

The human glucagon receptor (GCGR) belongs to the class B G protein-coupled receptor (GPCR) family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal structure of full-length GCGR containing both extracellular domain (ECD) and transmembrane domain (TMD) in an inactive conformation. The two domains are connected by a 12-residue segment termed the ‘stalk’, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of GCGR-TMD. The first extracellular loop (ECL1) exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure. Hydrogen/deuterium exchange, disulfide cross-linking and molecular dynamics studies suggest that the stalk and ECL1 play critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding about the signaling mechanisms of class B GPCRs. PMID:28514451

26 CFR 1.957-1 - Definition of controlled foreign corporation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... proportionate share of the corporate earnings, if the facts indicate that the shareholders of such other class..., and if a principal purpose of the arrangement is to avoid the classification of such foreign... corporate directors, and the owners of a majority of the class B stock are entitled to elect the other 4 of...

Fuel Injection Strategy for a Next Generation Pulse Detonation Engine

DTIC Science & Technology

2006-06-01

at 45°C CE Approved EMC EMC Directive 89/336/EEC; EN 61326-1 Emissions and Immunity Safety Low Voltage Directive 73/23/EEC; EN 61010 -1...Operating Humidity 0–90% Nonoperating Humidity 0–100% CDRH Class IIIb IEC Class 3B From www.mellesgriot.com 47 SILICON OPTICAL SENSOR Model

6 CFR 17.415 - Access to course offerings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... students on such basis, including health, physical education, industrial, business, vocational, technical, home economics, music, and adult education courses. (b)(1) With respect to physical education classes..., 2003. (2) This section does not prohibit grouping of students in physical education classes and...

28 CFR 54.415 - Access to course offerings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... basis, including health, physical education, industrial, business, vocational, technical, home economics, music, and adult education courses. (b)(1) With respect to classes and activities in physical education... September 29, 2000. (2) This section does not prohibit grouping of students in physical education classes...

Environmental Protection for Hazardous Materials Incidents. Volume 1. Hazardous Materials Incident Management System

DTIC Science & Technology

1990-11-01

radioactive) - Determine class of HAZMAT (Class A Explosive, Class B Explosive, Class C Explosive, Blasting Agent , Flammable Gas , Non- flammable Gas ... agent . Specific health and safety plans related to IRP actions amy be obtained from the same source. 2. Interaction of Fire Departments with the...such as digging near a gas line, a fuel tank, or buried explo- sives, the fire department would be briefed before beginning the work, and, under

[Root system distribution and biomechanical characteristics of Bambusa oldhami].

PubMed

Zhou, Ben-Zhi; Xu, Sheng-Hua; An, Yan-Fei; Xu, Sheng-Hua

2014-05-01

To determine the mechanism of soil stabilizing through Bambusa oldhami root system, the vertical distribution of B. oldhami root system in soil was investigated, and the tensile strength of individual root and soil shear strength were measured in B. oldhami forest. The dry mass, length, surface area and volume of the B. oldhami root system decreased with the increasing soil depth, with more than 90% of the root system occurring in the 0-40 cm soil layer. The root class with D 1 mm occupied the highest percentage of the total in terms of root length, accounting for 79.6%, but the lowest percentage of the total in terms of root volume, accounting for 8.2%. The root class with D >2 mm was the opposite, and the root class with D= 1-2 mm stayed in between. The maximum tensile resistance of B. oldhami root, either with 12% moisture content or a saturated moisture content, increased with the increasing root diameter, while the tensile strength decreased with the increasing root diameter in accordance with power function. Tensile strength of the root, with either of the two moisture contents, was significantly different among the diameter classes, with the highest tensile strength occurring in the root with D < or = 1 mm and the lowest in the root with D > or = 2 mm. The tensile strength of root with 12% moisture content was significantly higher than that with the saturated moisture content, and less effect of moisture content on root tensile strength would occur in thicker roots. The shear strengths of B. oldhami forest soil and of bare soil both increased with the increasing soil depth. The shear strength of B. oldhami forest soil had a linear positive correlation with the root content in soil, and was significantly higher than that of bare soil. The shear strength increment in B. oldhami forest was positively correlated with the root content in soil according to an exponential function, but not related significantly with soil depth.

Religious Practices in the Schools: Alternatives to the "Wall of Separation" Between Church and State.

ERIC Educational Resources Information Center

Thomas, Stephen B.

1981-01-01

The issue of the separation of church and state is explored, and compromises are offered to provide free exercise of religion without violating the Constitution. Suggested compromises include: (1) a moment of silence; (2) released time programs; (3) comparative religion classes; and (4) the use of the Bible in history and literature classes. (JN)

Teacher Trainees' Awareness Regarding Mother Tongue Use in English as a Foreign Language Classes

ERIC Educational Resources Information Center

Sener, Sabriye; Korkut, Perihan

2017-01-01

This study explores the views, perceptions and suggestions of teacher trainees regarding L1 use in foreign language classes and search for their awareness of the issue. A qualitative research design was employed. The data were gathered by means of 5 open-ended questions. The findings revealed that most of the participants preferred mostly target…

Forensic electrochemistry: the electroanalytical sensing of synthetic cathinone-derivatives and their accompanying adulterants in "legal high" products.

PubMed

Smith, Jamie P; Metters, Jonathan P; Irving, Craig; Sutcliffe, Oliver B; Banks, Craig E

2014-01-21

The production and abuse of new psychoactive substances, known as "legal highs" which mimic traditional drugs of abuse is becoming a global epidemic. Traditional analytical methodologies exist which can provide confirmatory analysis but there is a requirement for an on-the-spot analytical screening tool that could be used to determine whether a substance, or sample matrix contains such legal, or formally "legal highs". In this paper the electrochemical sensing of (±)-methcathinone and related compounds at a range of commercially available electrode substrates is explored. We demonstrate for the first time that this class of "legal highs" are electrochemically active providing a novel sensing protocol based upon their electrochemical oxidation. Screen-printed graphite sensing platforms are favoured due to their proven ability to be mass-produced providing large numbers of reliable and reproducible electrode sensing platforms that preclude the requirement of surface pre-treatment such as mechanical polishing as is the case in the use of solid/re-usable electrode substrates. Additionally they hold potential to be used on-site potentially being the basis of an on-site legal high screening device. Consequently the electroanalytical sensing of (±)-methcathinone (3a), (±)-4′-methylmethcathinone [3b, 4-MMC, (±)-mephedrone] and (±)-4′-methyl-N-ethylcathinone (3c, 4-MEC) is explored using screen-printed sensing platforms with the effect of pH explored upon the analytical response with their analytical efficiency evaluated towards the target legal highs. Interesting at pH values below 6 the voltammetric response quantitatively changes from that of an electrochemically irreversible response to that of a quasi-reversible signature which can be used analytically. It is demonstrated for the first time that the electroanalytical sensing of (±)-methcathinone (3a), (±)-mephedrone (3b) and 4-MEC (3c) are possible with accessible linear ranges found to correspond to 16–200 μg mL(−1) for 3a (at pH 12) and 16–350 μg mL(−1) for both 3b and 3c in pH 2, with limits of detection (3σ) found to correspond to 44.5, 39.8 and 84.2 μg mL(−1) respectively. Additionally adulterants that are commonly incorporated into cathinone legal highs are electrochemically explored at both pH 2 and 12.

A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

PubMed

Lum, R T; Kerwar, S S; Meyer, S M; Nelson, M G; Schow, S R; Shiffman, D; Wick, M M; Joly, A

1998-05-01

The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

49 CFR 173.133 - Assignment of packing group and hazard zones for Division 6.1 materials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pressure. Note 2: A liquid in Division 6.1 meeting criteria for Packing Group I, Hazard Zones A or B stated... 49 Transportation 2 2014-10-01 2014-10-01 false Assignment of packing group and hazard zones for... Group Assignments and Exceptions for Hazardous Materials Other Than Class 1 and Class 7 § 173.133...

49 CFR 173.133 - Assignment of packing group and hazard zones for Division 6.1 materials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pressure. Note 2: A liquid in Division 6.1 meeting criteria for Packing Group I, Hazard Zones A or B stated... 49 Transportation 2 2013-10-01 2013-10-01 false Assignment of packing group and hazard zones for... Group Assignments and Exceptions for Hazardous Materials Other Than Class 1 and Class 7 § 173.133...

DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia.

PubMed

Trajkovski, V; Spiroski, M

2015-01-01

In the present study, we report the first DNA analysis of HLA class I and class II alleles in Macedonian autistic subjects. We have analyzed the HLA-A, -C, -B, DRB1 genotypes of 35 autistic patients, and 98 healthy unrelated Macedonians (control group). HLA DNA typing of class I genes was performed using a Reverse Line Strip method (RLS), and the Sequencing Based Typing method (SBT) was used for typing of class II genes. In the autistic subjects for HLA-A locus 14 alleles have been identified with 2 being predominant *02 (25.7 %), and *24 (18.6 %). Among the 11 identified HLA-C alleles, 3 were predominant such as *12 (20.0 %), *07 (17.1 %), and *03 (12.9 %). Among the 18 identified HLA-B alleles, 2 were predominant: *51 (18.6 %), and *18 (11.4 %). For HLA-DRB1 locus, 10 alleles have been identified with 2 of them predominant such as: *11 (21.4 %), and *01 (14.3 %). The allele and haplotype frequencies in the patients group were compared to those of 98 control subjects. Our results showed significantly increased frequencies of HLA-C*03 (OR = 2.74*; χ2 = 4.68; p = 0.03), and HLA-DRB1*01 (OR = 3.10*; χ2 = 6.26; p = 0.012) alleles in autistic patients when compared to the controls. The most frequent haplotype frequencies in autistic sample were A*11-C*12-B*52-DRB1*15 (2.9 %), A*24-C*03-B*55-DRB1*16 (2.9 %), and A*24-C*03-B*55-DRB1*16 (2.9 %), but they were not statistically significant when compared to the control group. None of our patients carried allele or haplotype, which were protective in our population. Hardy-Weinberg equilibrium in autistic group showed that HLA-A (p < 0.03), HLA-C (p < 0.04), and HLA-DRB1 (p < 0.002) loci were in linkage disequilibria. In the control group, we found only for the HLA-DRB1 locus linkage disequilibrium (p < 0.002). Our results demonstrated the association of HLA-C*03 and HLA-DRB1*01 alleles with Macedonian autistic patients (Tab. 7, Ref. 37).

Patterns and predictors of violence against children in Uganda: a latent class analysis.

PubMed

Clarke, Kelly; Patalay, Praveetha; Allen, Elizabeth; Knight, Louise; Naker, Dipak; Devries, Karen

2016-05-24

To explore patterns of physical, emotional and sexual violence against Ugandan children. Latent class and multinomial logistic regression analysis of cross-sectional data. Luwero District, Uganda. In all, 3706 primary 5, 6 and 7 students attending 42 primary schools. To measure violence, we used the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool-Child Institutional. We used the Strengths and Difficulties Questionnaire to assess mental health and administered reading, spelling and maths tests. We identified three violence classes. Class 1 (N=696 18.8%) was characterised by emotional and physical violence by parents and relatives, and sexual and emotional abuse by boyfriends, girlfriends and unrelated adults outside school. Class 2 (N=975 26.3%) was characterised by physical, emotional and sexual violence by peers (male and female students). Children in Classes 1 and 2 also had a high probability of exposure to emotional and physical violence by school staff. Class 3 (N=2035 54.9%) was characterised by physical violence by school staff and a lower probability of all other forms of violence compared to Classes 1 and 2. Children in Classes 1 and 2 were more likely to have worked for money (Class 1 Relative Risk Ratio 1.97, 95% CI 1.54 to 2.51; Class 2 1.55, 1.29 to 1.86), been absent from school in the previous week (Class 1 1.31, 1.02 to 1.67; Class 2 1.34, 1.10 to 1.63) and to have more mental health difficulties (Class 1 1.09, 1.07 to 1.11; Class 2 1.11, 1.09 to 1.13) compared to children in Class 3. Female sex (3.44, 2.48 to 4.78) and number of children sharing a sleeping area predicted being in Class 1. Childhood violence in Uganda forms distinct patterns, clustered by perpetrator and setting. Research is needed to understand experiences of victimised children, and to develop mental health interventions for those with severe violence exposures. NCT01678846; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Exploring heterogeneity in clinical trials with latent class analysis

PubMed Central

Abarda, Abdallah; Contractor, Ateka A.; Wang, Juan; Dayton, C. Mitchell

2018-01-01

Case-mix is common in clinical trials and treatment effect can vary across different subgroups. Conventionally, a subgroup analysis is performed by dividing the overall study population by one or two grouping variables. It is usually impossible to explore complex high-order intersections among confounding variables. Latent class analysis (LCA) provides a framework to identify latent classes by observed manifest variables. Distal clinical outcomes and treatment effect can be different across these classes. This paper provides a step-by-step tutorial on how to perform LCA with R. A simulated dataset is generated to illustrate the process. In the example, the classify-analyze approach is employed to explore the differential treatment effects on distal outcomes across latent classes. PMID:29955579

A Zn-Dependent Metallopeptidase Is Responsible for Sensitivity to LsbB, a Class II Leaderless Bacteriocin of Lactococcus lactis subsp. lactis BGMN1-5

PubMed Central

Uzelac, Gordana; Lozo, Jelena; Aleksandrzak-Piekarczyk, Tamara; Gabrielsen, Christina; Kristensen, Tom; Nes, Ingolf F.; Diep, Dzung B.; Topisirovic, Ljubisa

2013-01-01

Lactococcus lactis subsp. lactis BGMN1-5 produces a leaderless class II bacteriocin called LsbB. To identify the receptor for LsbB, a cosmid library of the LsbB-sensitive strain BGMN1-596 was constructed. About 150 cosmid clones were individually isolated and transferred to LsbB-resistant mutants of BGMN1-596. Cosmid pAZILcos/MN2, carrying a 40-kb insert, was found to restore LsbB sensitivity in LsbB-resistant mutants. Further subcloning revealed that a 1.9-kb fragment, containing only one open reading frame, was sufficient to restore sensitivity. The fragment contains the gene yvjB coding for a Zn-dependent membrane-bound metallopeptidase, suggesting that this gene may serve as the receptor for LsbB. Further support for this notion derives from several independent experiments: (i) whole-genome sequencing confirmed that all LsbB-resistant mutants contain mutations in yvjB; (ii) disruption of yvjB by direct gene knockout rendered sensitive strains BGMN1-596 and IL1403 resistant to LsbB; and (iii) most compellingly, heterologous expression of yvjB in naturally resistant strains of other species, such as Lactobacillus paracasei and Enterococcus faecalis, also rendered them sensitive to the bacteriocin. To our knowledge, this is the first time a membrane-bound peptidase gene has been shown to be involved in bacteriocin sensitivity in target cells. We also demonstrated a novel successful approach for identifying bacteriocin receptors. PMID:24123824

Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes: HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese.

PubMed

Hamaguchi, K; Kimura, A; Seki, N; Higuchi, T; Yasunaga, S; Takahashi, M; Sasazuki, T; Kusuda, Y; Okeda, T; Itoh, K; Sakata, T

2000-01-01

Polymorphisms in the 5'-flanking region of the tumor necrosis factor (TNF)-alpha gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-alpha-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-alpha alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1*0405 or HLA-B54 allele, while the DRB1*0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1*0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese.

75 FR 17802 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc., Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-07

... Relating to Permitting Concurrent Listing of $3.50 and $4 Strikes for Classes in the $0.50 Strike and $1... (``Act''),\\1\\ and Rule 19b-4 \\2\\ thereunder, notice is hereby given that on March 30, 2010, NASDAQ OMX BX... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. \\3\\ 15 U.S.C. 78s(b)(3)(A). \\4\\ 17 CFR 240...

Characterisation of a type 1 Avian Paramyxovirus belonging to a divergent group.

PubMed

Briand, François-Xavier; Massin, Pascale; Jestin, Véronique

2014-01-10

Newcastle disease, induced by a type 1 Avian Paramyxovirus (APMV-1), is one of the most serious poultry diseases. APMV-1 are divided into two classes based on genetic analysis: class II strains have been recovered from wild or domestic birds and include virulent and avirulent isolates whereas class I strains have been mainly isolated from wild birds and are avirulent. Within class I, a new proposed genotype has recently been reported. The only full genome strain of this group is presently characterised from the point of view of codon usage with reference to class I and class II specificities. Class-specific residues were identified on HN and F proteins that are the two major proteins involved in cell attachment and pathogenicity. Comparison of protein patterns and codon usage for this newly identified APMV-1 strain indicates it is similar to class I viruses but contains a few characteristics close to the viruses of class II. Transmission of viruses from this recently identified divergent group from wild birds to domestic birds could have a major impact on the domestic poultry industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Distance Education: Analysis of Far- and Near-Site Interaction Patterns.

ERIC Educational Resources Information Center

Shih, Philip Hsi-Chang; Hara, Noriko; Li, Shaoqing; Yi, Qing

This paper reports on a study that explored the possibility of measuring distance education classes using the Media Sensor, a device designed to sample and record various electronic impulses generated during a distance education session. Research questions explored: (1) the ability of the Media Sensor to identify patterns in the audio and video…

Application of expert-notice dialogue (END) method to assess students’ science communication ability on biology

NASA Astrophysics Data System (ADS)

Sriyati, S.; Amelia, D. N.; Soniyana, G. T.

2018-05-01

Student’s science communication ability can be assessed by the Expert-Notice Dialogue (END) method which focusing on verbal explanations using graphs or images as a tool. This study aims to apply the END method to assess students’ science communication ability. The study was conducted in two high schools with each sample of one class at each school (A and B). The number of experts in class A is 8 students and 7 in class B, the number of notice in class A 24 students and 30 in class B. The material chosen for explanation by expert is Ecosystem in class A and plant classification in class B. Research instruments are rubric of science communication ability, observation rubric, notice concept test and notice questionnaire. The implementation recorded with a video camera and then transcribed based on rubric science communication ability. The results showed that the average of science communication ability in class A and B was 60% and 61.8%, respectively, in enough categories. Mastery of the notice concept is in good category with 79.10 averages in class A and 94.64 in class B. Through the questionnaire notice it is known that the END method generally helps notice in understanding the concept.

Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications

PubMed Central

Duke, Jamie L.; Xie, Hongbo M.; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J. D.; Kearns, Jane; Porter, David L.; Podsakoff, Gregory M.; Eisenlohr, Laurence C.; Biegel, Jaclyn A.; Chou, Stella T.; Monos, Dimitrios S.; Bessler, Monica; Olson, Timothy S.

2017-01-01

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by human leukocyte antigen (HLA)–restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole-exome sequencing (WES), we recently identified 2 patients with aAA with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the major histocompatibility complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping, we screened 66 patients with aAA for somatic HLA class I loss. We found somatic HLA loss in 11 patients (17%), with 13 loss-of-function mutations in HLA-A*33:03, HLA-A*68:01, HLA-B*14:02, and HLA-B*40:02 alleles. Three patients had more than 1 mutation targeting the same HLA allele. Interestingly, HLA-B*14:02 and HLA-B*40:02 were significantly overrepresented in patients with aAA compared with ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA and establishes a novel link between immunogenetics and clonal evolution of patients with aAA. PMID:28971166

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. Nicole Mann holds a tile sample as Christina Hammock, left, and Tyler "Nick" Hague look on. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. Josh Cassada holds a tile sample as Anne McClain, left, and Victor Glover look on. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. Participating in the briefing, from the left, are Andrew Morgan, Victor Glover, Anne McClain, Christina Hammock and Tyler "Nick" Hague. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

Intratympanic treatment of intractable unilateral Meniere disease: gentamicin or dexamethasone? A randomized controlled trial.

PubMed

Casani, Augusto Pietro; Piaggi, Paolo; Cerchiai, Niccolò; Seccia, Veronica; Franceschini, Stefano Sellari; Dallan, Iacopo

2012-03-01

To determine the efficacy and safety of low-dose intratympanic gentamicin (ITG) compared with intratympanic dexamethasone (ITD) in patients with intractable unilateral Ménière disease (MD). Open prospective randomized controlled study. Tertiary referral center. Sixty patients affected by definite unilateral MD were enrolled between January 1, 2007, and June 30, 2008. Thirty-two patients were treated with a buffered gentamicin solution injected in the middle ear (maximum of 2 injections); 28 patients were treated with ITD (4 mg/mL, 3 injections at intervals of 1 every 3 days). Mean outcome measurements consisted of control of vertigo attacks, pure tone average (PTA), speech discrimination score, functional disability score, and statistical analysis using repeated measures analysis of variance. In the ITG group at 2-year follow-up, complete control of vertigo (class A) was achieved in 26 patients (81%) and substantial control of vertigo (class B) in 4 patients (12.5%). In the ITD group, class A was achieved in 12 (43%), and class B in 5 (18%) patients. In the gentamicin group, 4 patients showed a reduction in PTA of ≥10 dB. In the ITD group, PTA was unchanged or slightly improved in 16 patients (belonging to class A-B) and worse in 12. Low-dose ITG achieved better outcome than ITD in the control of vertigo attacks in patients suffering from unilateral MD, with a very low incidence of hearing deterioration. ITD offers poorer vertigo control rate, and hearing preservation is achieved only in cases with no vertigo recurrences.

40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Class II Controlled Substances a B Appendix B to Subpart A of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED..., Subpt. A, App. B Appendix B to Subpart A of Part 82—Class II Controlled Substances a Controlled...

The global topography of Bennu: altimetry, photoclinometry, and processing

NASA Astrophysics Data System (ADS)

Perry, M. E.; Barnouin, O. S.; Daly, M. G.; Seabrook, J.; Palmer, E. E.; Gaskell, R. W.; Craft, K. L.; Roberts, J. H.; Philpott, L.; Asad, M. Al; Johnson, C. L.; Nair, A. H.; Espiritu, R. C.; Nolan, M. C.; Lauretta, D. S.

2017-09-01

The Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission will spend two years observing (101955) Bennu and will then return pristine samples of carbonaceous material from the asteroid [1]. Launched in September 2016, OSIRISREx arrives at Bennu in August 2018, acquires a sample in July 2020, and returns the sample to Earth in September 2023. The instruments onboard OSIRIS-REx will measure the physical and chemical properties of this B-class asteroid, a subclass within the larger group of C-complex asteroids that might be organic-rich. At approximately 500m in average diameter [2], Bennu is sufficiently large to retain substantial regolith and as an Apollo asteroid with a low inclination (6°), it is one of the most accessible primitive near-Earth asteroid.

Best uniform approximation to a class of rational functions

NASA Astrophysics Data System (ADS)

Zheng, Zhitong; Yong, Jun-Hai

2007-10-01

We explicitly determine the best uniform polynomial approximation to a class of rational functions of the form 1/(x-c)2+K(a,b,c,n)/(x-c) on [a,b] represented by their Chebyshev expansion, where a, b, and c are real numbers, n-1 denotes the degree of the best approximating polynomial, and K is a constant determined by a, b, c, and n. Our result is based on the explicit determination of a phase angle [eta] in the representation of the approximation error by a trigonometric function. Moreover, we formulate an ansatz which offers a heuristic strategies to determine the best approximating polynomial to a function represented by its Chebyshev expansion. Combined with the phase angle method, this ansatz can be used to find the best uniform approximation to some more functions.

Co-evolution of MHC class I and variable NK cell receptors in placental mammals.

PubMed

Guethlein, Lisbeth A; Norman, Paul J; Hilton, Hugo G; Parham, Peter

2015-09-01

Shaping natural killer (NK) cell functions in human immunity and reproduction are diverse killer cell immunoglobulin-like receptors (KIRs) that recognize polymorphic MHC class I determinants. A survey of placental mammals suggests that KIRs serve as variable NK cell receptors only in certain primates and artiodactyls. Divergence of the functional and variable KIRs in primates and artiodactyls predates placental reproduction. Among artiodactyls, cattle but not pigs have diverse KIRs. Catarrhine (humans, apes, and Old World monkeys) and platyrrhine (New World monkeys) primates, but not prosimians, have diverse KIRs. Platyrrhine and catarrhine systems of KIR and MHC class I are highly diverged, but within the catarrhines, a stepwise co-evolution of MHC class I and KIR is discerned. In Old World monkeys, diversification focuses on MHC-A and MHC-B and their cognate lineage II KIR. With evolution of C1-bearing MHC-C from MHC-B, as informed by orangutan, the focus changes to MHC-C and its cognate lineage III KIR. Evolution of C2 from C1 and fixation of MHC-C drove further elaboration of MHC-C-specific KIR, as exemplified by chimpanzee. In humans, the evolutionary trajectory changes again. Emerging from reorganization of the KIR locus and selective attenuation of KIR avidity for MHC class I are the functionally distinctive KIR A and KIR B haplotypes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Entry, Descent and Landing Systems Analysis: Exploration Class Simulation Overview and Results

NASA Technical Reports Server (NTRS)

DwyerCianciolo, Alicia M.; Davis, Jody L.; Shidner, Jeremy D.; Powell, Richard W.

2010-01-01

NASA senior management commissioned the Entry, Descent and Landing Systems Analysis (EDL-SA) Study in 2008 to identify and roadmap the Entry, Descent and Landing (EDL) technology investments that the agency needed to make in order to successfully land large payloads at Mars for both robotic and exploration or human-scale missions. The year one exploration class mission activity considered technologies capable of delivering a 40-mt payload. This paper provides an overview of the exploration class mission study, including technologies considered, models developed and initial simulation results from the EDL-SA year one effort.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

PubMed

Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans.

PubMed

McLaren, Paul J; Ripke, Stephan; Pelak, Kimberly; Weintrob, Amy C; Patsopoulos, Nikolaos A; Jia, Xiaoming; Erlich, Rachel L; Lennon, Niall J; Kadie, Carl M; Heckerman, David; Gupta, Namrata; Haas, David W; Deeks, Steven G; Pereyra, Florencia; Walker, Bruce D; de Bakker, Paul I W

2012-10-01

A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; P= 3.4 × 10(-18)] and B*81:01 (OR = 4.8; P= 1.3 × 10(-9)). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P = 1.2 × 10(-21)) and explains the signal of several HLA-B alleles, including B*57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus P= 2.8 × 10(-15)) in the canonical F pocket, position 63 in the B pocket (P= 1.5 × 10(-3)) and the non-pocket position 245 (P= 8.8 × 10(-10)), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of HLA-B in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control.

Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group.

PubMed

Jaeger, Veronika K; Distler, Oliver; Maurer, Britta; Czirják, Laszlo; Lóránd, Veronika; Valentini, Gabriele; Vettori, Serena; Del Galdo, Francesco; Abignano, Giuseppina; Denton, Christopher; Nihtyanova, Svetlana; Allanore, Yannick; Avouac, Jerome; Riemekasten, Gabriele; Siegert, Elise; Huscher, Dörte; Matucci-Cerinic, Marco; Guiducci, Serena; Frerix, Marc; Tarner, Ingo H; Garay Toth, Beata; Fankhauser, Beat; Umbricht, Jörg; Zakharova, Anastasia; Mihai, Carina; Cozzi, Franco; Yavuz, Sule; Hunzelmann, Nicolas; Rednic, Simona; Vacca, Alessandra; Schmeiser, Tim; Riccieri, Valeria; García de la Peña Lefebvre, Paloma; Gabrielli, Armando; Krummel-Lorenz, Brigitte; Martinovic, Duska; Ancuta, Codrina; Smith, Vanessa; Müller-Ladner, Ulf; Walker, Ulrich A

2018-03-01

The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

10 CFR 1042.415 - Access to course offerings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... health, physical education, industrial, business, vocational, technical, home economics, music, and adult education courses. (b)(1) With respect to classes and activities in physical education at the elementary... event later than one year from February 20, 2001. With respect to physical education classes and...

41 CFR 101-4.415 - Access to course offerings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... basis, including health, physical education, industrial, business, vocational, technical, home economics, music, and adult education courses. (b)(1) With respect to classes and activities in physical education... September 29, 2000. (2) This section does not prohibit grouping of students in physical education classes...

49 CFR 25.415 - Access to course offerings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... health, physical education, industrial, business, vocational, technical, home economics, music, and adult education courses. (b)(1) With respect to classes and activities in physical education at the elementary... event later than one year from September 29, 2000. With respect to physical education classes and...

21 CFR 884.1700 - Hysteroscopic insufflator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... with a hysteroscope. (b) Classification. (1) Class II (performance standards). (2) Class I for tubing and tubing/filter fits which only include accessory instruments that are not used to effect intrauterine access, e.g., hysteroscopic introducer sheaths, etc.; and single-use tubing kits used for only...

A More Efficient Contextuality Distillation Protocol

NASA Astrophysics Data System (ADS)

Meng, Hui-xian; Cao, Huai-xin; Wang, Wen-hua; Fan, Ya-jing; Chen, Liang

2018-03-01

Based on the fact that both nonlocality and contextuality are resource theories, it is natural to ask how to amplify them more efficiently. In this paper, we present a contextuality distillation protocol which produces an n-cycle box B ∗ B ' from two given n-cycle boxes B and B '. It works efficiently for a class of contextual n-cycle ( n ≥ 4) boxes which we termed as "the generalized correlated contextual n-cycle boxes". For any two generalized correlated contextual n-cycle boxes B and B ', B ∗ B ' is more contextual than both B and B '. Moreover, they can be distilled toward to the maximally contextual box C H n as the times of iteration goes to infinity. Among the known protocols, our protocol has the strongest approximate ability and is optimal in terms of its distillation rate. What is worth noting is that our protocol can witness a larger set of nonlocal boxes that make communication complexity trivial than the protocol in Brunner and Skrzypczyk (Phys. Rev. Lett. 102, 160403 2009), this might be helpful for exploring the problem that why quantum nonlocality is limited.

A More Efficient Contextuality Distillation Protocol

NASA Astrophysics Data System (ADS)

Meng, Hui-xian; Cao, Huai-xin; Wang, Wen-hua; Fan, Ya-jing; Chen, Liang

2017-12-01

Based on the fact that both nonlocality and contextuality are resource theories, it is natural to ask how to amplify them more efficiently. In this paper, we present a contextuality distillation protocol which produces an n-cycle box B ∗ B ' from two given n-cycle boxes B and B '. It works efficiently for a class of contextual n-cycle (n ≥ 4) boxes which we termed as "the generalized correlated contextual n-cycle boxes". For any two generalized correlated contextual n-cycle boxes B and B ', B ∗ B ' is more contextual than both B and B '. Moreover, they can be distilled toward to the maximally contextual box C H n as the times of iteration goes to infinity. Among the known protocols, our protocol has the strongest approximate ability and is optimal in terms of its distillation rate. What is worth noting is that our protocol can witness a larger set of nonlocal boxes that make communication complexity trivial than the protocol in Brunner and Skrzypczyk (Phys. Rev. Lett. 102, 160403 2009), this might be helpful for exploring the problem that why quantum nonlocality is limited.

Class, Identity, and Teacher Education

ERIC Educational Resources Information Center

Van Galen, Jane A.

2010-01-01

This paper explores the possibilities of working with White, working-class teacher education students to explore the "complex social trajectory" (Reay in Women's Stud Int Forum 20(2):225-233, 1997a, p. 19) of class border crossing as they progress through college. Through analysis of a course that I have developed, "Education and the American…

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

2011-01-01

This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

Design of non-selective refocusing pulses with phase-free rotation axis by gradient ascent pulse engineering algorithm in parallel transmission at 7T.

PubMed

Massire, Aurélien; Cloos, Martijn A; Vignaud, Alexandre; Le Bihan, Denis; Amadon, Alexis; Boulant, Nicolas

2013-05-01

At ultra-high magnetic field (≥ 7T), B1 and ΔB0 non-uniformities cause undesired inhomogeneities in image signal and contrast. Tailored radiofrequency pulses exploiting parallel transmission have been shown to mitigate these phenomena. However, the design of large flip angle excitations, a prerequisite for many clinical applications, remains challenging due the non-linearity of the Bloch equation. In this work, we explore the potential of gradient ascent pulse engineering to design non-selective spin-echo refocusing pulses that simultaneously mitigate severe B1 and ΔB0 non-uniformities. The originality of the method lays in the optimization of the rotation matrices themselves as opposed to magnetization states. Consequently, the commonly used linear class of large tip angle approximation can be eliminated from the optimization procedure. This approach, combined with optimal control, provides additional degrees of freedom by relaxing the phase constraint on the rotation axis, and allows the derivative of the performance criterion to be found analytically. The method was experimentally validated on an 8-channel transmit array at 7T, using a water phantom with B1 and ΔB0 inhomogeneities similar to those encountered in the human brain. For the first time in MRI, the rotation matrix itself on every voxel was measured by using Quantum Process Tomography. The results are complemented with a series of spin-echo measurements comparing the proposed method against commonly used alternatives. Both experiments confirm very good performance, while simultaneously maintaining a low energy deposition and pulse duration compared to well-known adiabatic solutions. Copyright © 2013 Elsevier Inc. All rights reserved.

B Cells and Humoral Immunity in Atherosclerosis

PubMed Central

Tsiantoulas, Dimitrios; Diehl, Cody J.; Witztum, Joseph L.; Binder, Christoph J.

2014-01-01

Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our understanding of this disease. Although the role of T cells has been extensively studied for decades, only recently has the role of B cells gained more attention. Recent studies have identified differential effects of different B-cell subsets and helped to clarify the still poorly understood mechanisms by which these act. B1 cells have been shown to prevent lesion formation, whereas B2 cells have been suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells, have been shown to mediate atheroprotective effects, but the functional role of other immunoglobulin classes, particularly IgG, still remains elusive. In this review, we will focus on recent insights on the role of B cells and various immunoglobulin classes and how these may mediate their effects in atherosclerotic lesion formation. Moreover, we will highlight potential therapeutic approaches focusing on B-cell depletion that could be used to translate experimental evidence to human disease. PMID:24855199

On the perturbation of the group generalized inverse for a class of bounded operators in Banach spaces

NASA Astrophysics Data System (ADS)

Castro-González, N.; Vélez-Cerrada, J. Y.

2008-05-01

Given a bounded operator A on a Banach space X with Drazin inverse AD and index r, we study the class of group invertible bounded operators B such that I+AD(B-A) is invertible and . We show that they can be written with respect to the decomposition as a matrix operator, , where B1 and are invertible. Several characterizations of the perturbed operators are established, extending matrix results. We analyze the perturbation of the Drazin inverse and we provide explicit upper bounds of ||B#-AD|| and ||BB#-ADA||. We obtain a result on the continuity of the group inverse for operators on Banach spaces.

On Identifying Clusters Within the C-type Asteroids of the Sloan Digital Sky Survey

NASA Astrophysics Data System (ADS)

Poole, Renae; Ziffer, J.; Harvell, T.

2012-10-01

We applied AutoClass, a data mining technique based upon Bayesian Classification, to C-group asteroid colors in the Sloan Digital Sky Survey (SDSS). Previous taxonomic studies relied mostly on Principal Component Analysis (PCA) to differentiate asteroids within the C-group (e.g. B, G, F, Ch, Cg and Cb). AutoClass's advantage is that it calculates the most probable classification for us, removing the human factor from this part of the analysis. In our results, AutoClass divided the C-groups into two large classes and six smaller classes. The two large classes (n=4974 and 2033, respectively) display distinct regions with some overlap in color-vs-color plots. Each cluster's average spectrum is compared to 'typical' spectra of the C-group subtypes as defined by Tholen (1989) and each cluster's members are evaluated for consistency with previous taxonomies. Of the 117 asteroids classified as B-type in previous taxonomies, only 12 were found with SDSS colors that matched our criteria of having less than 0.1 magnitude error in u and 0.05 magnitude error in g, r, i, and z colors. Although this is a relatively small group, 11 of the 12 B-types were placed by AutoClass in the same cluster. By determining the C-group sub-classifications in the large SDSS database, this research furthers our understanding of the stratigraphy and composition of the main-belt.

HIV-1 evades virus-specific IgG2 and IgA class switching by targeting systemic and intestinal B cells via long-range intercellular conduits

PubMed Central

Xu, Weifeng; Santini, Paul A.; Sullivan, John S.; He, Bing; Shan, Meimei; Ball, Susan C.; Dyer, Wayne B.; Ketas, Thomas J.; Chadburn, Amy; Cohen-Gould, Leona; Knowles, Daniel M.; Chiu, April; Sanders, Rogier W.; Chen, Kang; Cerutti, Andrea

2009-01-01

Contact-dependent communication between immune cells generates protection, but also facilitates viral spread. We found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type-1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients harboring Nef-deficient virions, our data suggest that HIV-1 exploits intercellular highways as a “Trojan horse” to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry. PMID:19648924

Flower development of Phalaenopsis orchid involves functionally divergent SEPALLATA-like genes

PubMed Central

Pan, Zhao-Jun; Chen, You-Yi; Du, Jian-Syun; Chen, Yun-Yu; Chung, Mei-Chu; Tsai, Wen-Chieh; Wang, Chun-Neng; Chen, Hong-Hwa

2014-01-01

The Phalaenopsis orchid produces complex flowers that are commercially valuable, which has promoted the study of its flower development. E-class MADS-box genes, SEPALLATA (SEP), combined with B-, C- and D-class MADS-box genes, are involved in various aspects of plant development, such as floral meristem determination, organ identity, fruit maturation, seed formation and plant architecture. Four SEP-like genes were cloned from Phalaenopsis orchid, and the duplicated PeSEPs were grouped into PeSEP1/3 and PeSEP2/4. All PeSEPs were expressed in all floral organs. PeSEP2 expression was detectable in vegetative tissues. The study of protein–protein interactions suggested that PeSEPs may form higher order complexes with the B-, C-, D-class and AGAMOUS LIKE6-related MADS-box proteins to determine floral organ identity. The tepal became a leaf-like organ when PeSEP3 was silenced by virus-induced silencing, with alterations in epidermis identity and contents of anthocyanin and chlorophyll. Silencing of PeSEP2 had minor effects on the floral phenotype. Silencing of the E-class genes PeSEP2 and PeSEP3 resulted in the downregulation of B-class PeMADS2-6 genes, which indicates an association of PeSEP functions and B-class gene expression. These findings reveal the important roles of PeSEP in Phalaenopsis floral organ formation throughout the developmental process by the formation of various multiple protein complexes. PMID:24571782

Self-Assembled Multi-Component Catenanes: Structural Insights into an Adaptable Class of Molecular Receptors and [2]-Catenanes

DTIC Science & Technology

2012-06-11

V fragmentor setting, the targeted MS1 ion was the singly charged ion [1b2 F22 + H] + (m/z = 1626.7100). For DSA reaction mixtures containing F4b and...the basis of its high abundance under the electrospray conditions. Both analyses showed two tetrameric daughter ions ([1b3 F21 + H] + and [1b2 F22 ...dimeric daughter ion [ F22 + H] + (Scheme 2), which only occurs in the non-alternating [1b2 F22 ] structure, was observed in both cases, but with only

46 CFR 116.415 - Fire control boundaries.

Code of Federal Regulations, 2013 CFR

2013-10-01

... conditions are met: (1) The space in question is surrounded by A-Class divisions or extends to the outer... various spaces must meet the requirements of Table 116.415(b). Table 116.415 (b)—Bulkheads Spaces (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) Control Space (1) B-0 A-0 A-0 A-0 A-15 A-60 A-60 A-0...

46 CFR 170.255 - Class 1 doors; permissible locations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... point at side, is at least 7 feet (2.14 meters) above the deepest load line. (b) Class 1 doors are..., the door is in a location where it will be closed at all times except when actually in use; and (2... lowest point at side is less than 7 feet (2.14 meters) above the deepest load line, an indicator light...

Requirement of 8-mercaptoguanosine as a costimulus for IL-4-dependent mu to gamma1 class switch recombination in CD38-activated B cells.

PubMed

Tsukamoto, Yumiko; Uehara, Shoji; Mizoguchi, Chieko; Sato, Atsushi; Horikawa, Keisuke; Takatsu, Kiyoshi

2005-10-21

Mature B-2 cells expressing surface IgM and IgD proliferate upon stimulation by CD38, CD40 or lipopolysaccharide (LPS) and differentiate into IgG1-producing plasma cells in the presence of cytokines. The process of class switch recombination (CSR) from IgM to other isotypes is highly regulated by cytokines and activation-induced cytidine deaminase (AID). Blimp-1 and XBP-1 play an essential role in the terminal differentiation of switched B-2 cells to Ig-producing plasma cells. IL-5 induces AID and Blimp-1 expression in CD38- and CD40-activated B-2 cells, leading to mu to gamma1 CSR at DNA level and IgG1 production. IL-4, a well-known IgG1-inducing factor, does not induce mu to gamma1 CSR in CD38-activated B-2 cells or Blimp-1, while IL-4 induces mu to gamma1 CSR, XBP-1 expression, and IgG1 production expression in CD40-activated B-2 cells. Interestingly, the addition of 8-mercaptoguanosine (8-SGuo) with IL-4 to the culture of CD38-activated B cells can induce mu to gamma1 CSR, Blimp-1 expression, and IgG1 production. Intriguingly, 8-SGuo by itself induces AID expression in CD38-activated B cells. However, it does not induce mu to gamma1 CSR. These results imply that the mode of B-cell activation for extracellular stimulation affects the outcome of cytokine stimulation with respect to the efficiency and direction of CSR, and the requirements of the transcriptional regulator and the generation of antibody-secreting cells. Furthermore, our data suggest the requirement of additional molecules in addition to AID for CSR.

Distribution of HLA class I alleles and haplotypes in Korean.

PubMed Central

Kim, T. G.; Han, H.; Lim, B. U.; Kim, W.; Kim, S. M.

1993-01-01

The antigen (phenotype), gene (allele) and haplotype frequencies of HLA class I were analysed in 4,622 Koreans. With allele frequencies of over 0.05, the most frequent HLA-A,-B and -C antigens were A2, A24, A33, A11, A26, A31; B62, B51, B44, B54, B61, B35, B58, B60; Cw3, Cw1, Cw4, Cw7. Of these A2, A24, Cw1 and Cw3 were present in very high frequencies, respectively (0.3211, 0.2200, 0.2204, and 0.3737). The most common haplotypes with frequencies larger than 0.02 were A2-Blank, A33-B44, A33-B58, A11-B62, A24-B51, A24-B54, A2-B27, B54-Cw1, B58-Cw3, B51-Blank, B61-Cw3, B62-Cw4, B35-Cw3, B44-Blank, B60-Cw3, B27-Cw1, A2-Cw3, A2-Cw1, A24-Cw1, A33-Cw3, A26-Cw3, and A11-Cw4. A significant negative linkage disequilibrium was found for the haplotypes of A2-B7, A2-B44, A2-B58, A24-B13, A24-B27, A33-B54 and A33-B62, of which frequencies were larger than 0.003. The B-C and A-C haplotypes which showed the significant negative linkage disequilibrium were B44-Cw1, B51-Cw1, B44-Cw3,B62-Blank, A2-Cw4, A2-Blank, A11-Cw3, A11-Blank and A33-Cw1 and had frequencies higher than 0.01. The findings presented here could be used per se to estimate the populational relationships or as the control data for HLA-disease investigation. Furthermore they could provide the scope for the definition of new antigens. PMID:8240747

Constitutive CD40L Expression on B Cells Prematurely Terminates Germinal Center Response and Leads to Augmented Plasma Cell Production in T Cell Areas

PubMed Central

Bolduc, Anna; Long, Eugene; Stapler, Dale; Cascalho, Marilia; Tsubata, Takeshi; Koni, Pandelakis A.; Shimoda, Michiko

2013-01-01

CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T–B interaction in the generation of germinal center and memory B cells is still incompletely understood. To address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice with B cell-restricted MHC class II deficiency. Using this mouse model, we show that constitutive CD40L expression on B cells alone could not induce germinal center differentiation of MHC class II-deficient B cells after immunization with T cell-dependent Ag. Thus, some other MHC class II-dependent T cell-derived signals are essential for the generation of germinal center B cells in response to T cell-dependent Ag. In fact, CD40LBTg mice generated a complex Ag-specific IgG1 response, which was greatly enhanced in early, but reduced in late, primary response compared with control mice. We also found that the frequency of Ag-specific germinal center B cells in CD40LBTg mice was abruptly reduced 1 wk after immunization. As a result, the numbers of Ag-specific IgG1 long-lived plasma cells and memory B cells were reduced. By histology, large numbers of Ag-specific plasma cells were found in T cell areas adjacent to Ag-specific germinal centers of CD40LBTg mice, temporarily during the second week of primary response. These results indicate that CD40L expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells. Our results support the notion that CD40 signaling is an active termination signal for germinal center reaction. PMID:20505142

Williams Air Force Base Air Quality Monitoring Study,

DTIC Science & Technology

1980-07-01

34 ’ ." " PERCENT OCCURRENCE SPEED CLASSES ( MPS1 Figure 17. Annual wind rose at station 4, WAFB, from June 1976 to June 1977. 47 NAF6 TRAILER 5 JULY 76...rHRU JUNE 77 a 20 0. 00 500 1b000 I’s00 700 PERCENT OCCURRENCE SPEED CLASSES ( MPS1 Figure 18. Annual wind rose at station 5, WAFB, from June 1976 to

49 CFR 176.400 - Stowage of Division 1.5, Class 4 (flammable solids) and Class 5 (oxidizers and organic peroxides...

Code of Federal Regulations, 2010 CFR

2010-10-01

... reasonably practicable and be stowed away from all sources of heat and ignition. (b) Division 5.2 (organic peroxide) material must be stowed away from living quarters or access to them. Division 5.2 (organic...

Clinical classes of injured workers with chronic low back pain: a latent class analysis with relationship to working status.

PubMed

Carlesso, Lisa C; Raja Rampersaud, Y; Davis, Aileen M

2018-01-01

To determine (a) clinical classes of injured workers with chronic low back pain (CLBP), (b) predictors of class membership and (c) associations of classes with baseline work status. Patients with CLBP from a tertiary care outpatient clinic in Toronto, Canada were sampled. Latent class analysis was applied to determine class structure using physical, psychological and coping indicators. Classes were interpreted by class-specific means and analyzed for predictors of membership. Lastly, association of the classes with being off work was modeled. A 3-class model was chosen based on fit criteria, theoretical and clinical knowledge of this population. The resultant 3 classes represented low, moderate and high levels of clinical severity. Predictors of being in the high severity group compared to the low severity group were < high school education [odds ratio (OR) 3.06, 95% CI (1.47, 6.37)] and comorbidity total [OR 1.28, 95% CI (1.03, 1.59)]. High severity class membership was associated with four times increased risk of being off work at baseline compared to those in the low severity group [OR 3.98, 95% CI (1.61, 6.34)]. In a cohort of injured workers with CLBP, 3 clinical classes were identified with distinct psychological and physical profiles. These profiles are useful in aiding clinicians to identify patients of high clinical severity who may be potentially at risk for problematic return to work.

Rev1 Recruits Ung to Switch Regions and Enhances dU Glycosylation for Immunoglobulin Class Switch DNA Recombination

PubMed Central

Zan, Hong; White, Clayton A.; Thomas, Lisa M.; Mai, Thach; Li, Guideng; Xu, Zhenming; Zhang, Jinsong; Casali, Paolo

2012-01-01

SUMMARY By diversifying the biological effector functions of antibodies, class switch DNA recombination (CSR) plays a critical role in the maturation of the immune response. It is initiated by AID-mediated dC deamination, yielding dUs, and dU glycosylation by Ung in antibody switch (S) region DNA. Here we showed that the translesion DNA synthesis polymerase Rev1 directly interacted with Ung and targeted in an AID-dependent and Ung-independent fashion the S regions undergoing CSR. Rev1–/– Ung+/+ B cells reduced Ung recruitment to S regions, DNA-dU glycosylation and CSR. This together with an S region spectrum of mutations similar to that of Rev1+/+ Ung–/– B cells suggested that Rev1 operated in the same pathway as Ung, as emphasized by further decreased CSR in Rev1–/– Msh2–/– B cells. Rescue of CSR in Rev1–/– B cells by a catalytically inactive Rev1 mutant showed that the important role of Rev1 in CSR is mediated by Rev1 scaffold, not enzymatic function. PMID:23140944

Hepatic Overexpression of Endothelial Lipase Lowers HDL (High-Density Lipoprotein) but Maintains Reverse Cholesterol Transport in Mice: Role of SR-BI (Scavenger Receptor Class B Type I)/ABCA1 (ATP-Binding Cassette Transporter A1)-Dependent Pathways.

PubMed

Takiguchi, Shunichi; Ayaori, Makoto; Yakushiji, Emi; Nishida, Takafumi; Nakaya, Kazuhiro; Sasaki, Makoto; Iizuka, Maki; Uto-Kondo, Harumi; Terao, Yoshio; Yogo, Makiko; Komatsu, Tomohiro; Ogura, Masatsune; Ikewaki, Katsunori

2018-05-10

Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma 3 H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal 3 H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of 3 HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived 3 H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol. Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways. © 2018 American Heart Association, Inc.

Combined Patterns of Risk for Problem and Obesogenic Behaviors in Adolescents: A Latent Class Analysis Approach

ERIC Educational Resources Information Center

Fleary, Sasha A.

2017-01-01

Background: Several studies have used latent class analyses to explore obesogenic behaviors and substance use in adolescents independently. We explored a variety of health risks jointly to identify distinct patterns of risk behaviors among adolescents. Methods: Latent class models were estimated using Youth Risk Behavior Surveillance System…

An Analysis of the Ticonderoga Class Guided Missile Cruisers 1B1B Account

DTIC Science & Technology

2008-12-01

and shapes 96 Ores, minerals , and their primary products 97 Unassigned 98 Unassigned 99 Miscellaneous 30 THIS PAGE INTENTIONALLY LEFT BLANK... flotation vests, which totaled $29,137. Table 90. 2006 Expense Element “W” Sustainment Phase Expenditures Ship Total Months in Phase Mean Per

Generation of tricyclic imidazo[1,2-a]pyrazines as novel PI3K inhibitors by application of a conformational restriction strategy.

PubMed

Martínez González, Sonia; Rodríguez-Arístegui, Sonsoles; Hernández, Ana Isabel; Varela, Carmen; González Cantalapiedra, Esther; Álvarez, Rosa María; Rodríguez Hergueta, Antonio; Bischoff, James R; Albarrán, María Isabel; Cebriá, Antonio; Cendón, Elena; Cebrián, David; Alfonso, Patricia; Pastor, Joaquín

2017-06-01

The involvement of the phosphoinositide 3-kinases (PI3Ks) in several diseases, especially in the oncology area, has singled it as one of the most explored therapeutic targets in the last two decades. Many different inhibitor classes have been developed by the industry and academia with a diverse selectivity profile within the PI3K family. In the present manuscript we report a further exploration of our lead PI3K inhibitor ETP-46321 (Martínez González et al., 2012) 1 by the application of a conformational restriction strategy. For that purpose we have successfully synthesized novel tricyclic imidazo[1,2-a]pyrazine derivatives as PI3K inhibitors. This new class of compounds had enable the exploration of the solvent-accessible region within PI3K and resulted in the identification of molecule 8q with the best selectivity PI3Kα/δ isoform profile in vitro, and promising in vivo PK data. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Gentles, Robert G.; Sheriff, Steven; Beno, Brett R.

Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.

High-value components and bioactives from sea cucumbers for functional foods--a review.

PubMed

Bordbar, Sara; Anwar, Farooq; Saari, Nazamid

2011-01-01

Sea cucumbers, belonging to the class Holothuroidea, are marine invertebrates, habitually found in the benthic areas and deep seas across the world. They have high commercial value coupled with increasing global production and trade. Sea cucumbers, informally named as bêche-de-mer, or gamat, have long been used for food and folk medicine in the communities of Asia and Middle East. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as Vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin), and minerals, especially calcium, magnesium, iron and zinc. A number of unique biological and pharmacological activities including anti-angiogenic, anticancer, anticoagulant, anti-hypertension, anti-inflammatory, antimicrobial, antioxidant, antithrombotic, antitumor and wound healing have been ascribed to various species of sea cucumbers. Therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives especially triterpene glycosides (saponins), chondroitin sulfates, glycosaminoglycan (GAGs), sulfated polysaccharides, sterols (glycosides and sulfates), phenolics, cerberosides, lectins, peptides, glycoprotein, glycosphingolipids and essential fatty acids. This review is mainly designed to cover the high-value components and bioactives as well as the multiple biological and therapeutic properties of sea cucumbers with regard to exploring their potential uses for functional foods and nutraceuticals.

High-Value Components and Bioactives from Sea Cucumbers for Functional Foods—A Review

PubMed Central

Bordbar, Sara; Anwar, Farooq; Saari, Nazamid

2011-01-01

Sea cucumbers, belonging to the class Holothuroidea, are marine invertebrates, habitually found in the benthic areas and deep seas across the world. They have high commercial value coupled with increasing global production and trade. Sea cucumbers, informally named as bêche-de-mer, or gamat, have long been used for food and folk medicine in the communities of Asia and Middle East. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as Vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin), and minerals, especially calcium, magnesium, iron and zinc. A number of unique biological and pharmacological activities including anti-angiogenic, anticancer, anticoagulant, anti-hypertension, anti-inflammatory, antimicrobial, antioxidant, antithrombotic, antitumor and wound healing have been ascribed to various species of sea cucumbers. Therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives especially triterpene glycosides (saponins), chondroitin sulfates, glycosaminoglycan (GAGs), sulfated polysaccharides, sterols (glycosides and sulfates), phenolics, cerberosides, lectins, peptides, glycoprotein, glycosphingolipids and essential fatty acids. This review is mainly designed to cover the high-value components and bioactives as well as the multiple biological and therapeutic properties of sea cucumbers with regard to exploring their potential uses for functional foods and nutraceuticals. PMID:22072996

NASA Instrument Cost Model for Explorer-Like Mission Instruments (NICM-E)

NASA Technical Reports Server (NTRS)

Habib-Agahi, Hamid; Fox, George; Mrozinski, Joe; Ball, Gary

2013-01-01

NICM-E is a cost estimating relationship that supplements the traditional NICM System Level CERs for instruments flown on NASA Explorer-like missions that have the following three characteristics: 1) fly on Class C missions, 2) major development led and performed by universities or research foundations, and 3) have significant level of inheritance.

Exploring Flipboard to Support Coursework: Student Beliefs, Attitudes, Engagement, and Device Choice

ERIC Educational Resources Information Center

Hornik, Steven; deNoyelles, Aimee; Chen, Baiyun

2016-01-01

The purpose of the study is to explore the use of a mobile application called Flipboard, which facilitates the curation of digital content into a magazine-like product, to engage students in class discussion and participation in a college course. Research questions include: (1) What were students' beliefs and attitudes regarding the use of…

Single agent and synergistic combinatorial efficacy of first-in-class small molecule imipridone ONC201 in hematological malignancies.

PubMed

Prabhu, Varun V; Talekar, Mala K; Lulla, Amriti R; Kline, C Leah B; Zhou, Lanlan; Hall, Junior; Van den Heuvel, A Pieter J; Dicker, David T; Babar, Jawad; Grupp, Stephan A; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Pu, Jeffrey J; Claxton, David F; Khan, Nadia; Oster, Wolfgang; Allen, Joshua E; El-Deiry, Wafik S

2018-01-01

ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples. ONC201 induced caspase-dependent apoptosis that involved activation of the integrated stress response (ATF4/CHOP) pathway, inhibition of Akt phosphorylation, Foxo3a activation, downregulation of cyclin D1, IAP and Bcl-2 family members. ONC201 synergistically reduced cell viability in combination with cytarabine and 5-azacytidine in AML cells. ONC201 combined with cytarabine in a Burkitt's lymphoma xenograft model induced tumor growth inhibition that was superior to either agent alone. ONC201 synergistically combined with bortezomib in MM, MCL and ALCL cells and with ixazomib or dexamethasone in MM cells. ONC201 combined with bortezomib in a Burkitt's lymphoma xenograft model reduced tumor cell density and improved CHOP induction compared to either agent alone. These results serve as a rationale for ONC201 single-agent trials in relapsed/refractory acute leukemia, non-Hodgkin's lymphoma, MM and combination trial with dexamethasone in MM, provide pharmacodynamic biomarkers and identify further synergistic combinatorial regimens that can be explored in the clinic.

Concept of Operations Evaluation for Using Remote-Guidance Ultrasound for Exploration Spaceflight.

PubMed

Hurst, Victor W; Peterson, Sean; Garcia, Kathleen; Ebert, Douglas; Ham, David; Amponsah, David; Dulchavsky, Scott

2015-12-01

Remote-guidance (RG) techniques aboard the International Space Station (ISS) have enabled astronauts to collect diagnostic-level ultrasound (US) images. Exploration-class missions will likely require nonformally trained sonographers to operate with greater autonomy given longer communication delays (> 6 s for missions beyond the Moon) and blackouts. Training requirements for autonomous collection of US images by non-US experts are being determined. Novice US operators were randomly assigned to one of three groups to collect standardized US images while drawing expertise from A) RG only, B) a computer training tool only, or C) both RG and a computer training tool. Images were assessed for quality and examination duration. All operators were given a 10-min standardized generic training session in US scanning. The imaging task included: 1) bone fracture assessment in a phantom and 2) Focused Assessment with Sonography in Trauma (FAST) examination in a healthy volunteer. A human factors questionnaire was also completed. Mean time for group B during FAST was shorter (20.4 vs. 22.7 min) than time for the other groups. Image quality scoring was lower than in groups A or C, but all groups produced images of acceptable diagnostic quality. RG produces US images of higher quality than those produced with only computer-based instruction. Extended communication delays in exploration missions will eliminate the option of real-time guidance, thus requiring autonomous operation. The computer program used appears effective and could be a model for future digital US expertise banks. Terrestrially, it also provides adequate self-training and mentoring mechanisms.

Clinical, immunologic and insulin secretory characteristics of young black South African patients with diabetes: Hospital based single centre study.

PubMed

Ekpebegh, C O; Longo-Mbenza, B

2013-03-01

To classify and characterize the clinical features of various diabetes classes among young black South Africans. Cross sectional study of 60 black patients with diabetes, all less than 30 years of age and attending Nelson Mandela Academic Hospital, Mthatha, South Africa. Diabetes was classified as Types 1A, 1B and 2 based on the anti-glutamic acid decarboxylase status and serum C-peptide response to intravenous injection of glucagon. Mean age was 19.6±4.8 years (n=60) with similar gender distribution. The mean duration of diabetes was 24.2±45.1 months. Type 1A was the class of diabetes in 55% (n=33/60) of patients. Type 1B and 2 accounted for 30% (n=18/60) and 15% (n=9/60) of patients respectively. Patients classified as Type 2 had higher waist circumference and higher prevalence of acanthosis nigricans than Types 1A and 1B groups. History of diabetes in a first degree relative and hypertension were found in similar proportions of patients with Types 1A, 1B and 2 diabetes. Five Type 1A diabetes patients had body mass index of 26.2-41kg/m(2) and this included two newly diagnosed patients with body mass index of 26.7kg/m(2) and 33.2kg/m(2). The majority of our young black South Africans with diabetes are of the Type 1A class. Acanthosis nigricans was not found in any patient with Type 1 A diabetes. A minority of Type 1 A diabetes patients were obese at initial diagnosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Counting Heron Triangles with Constraints

DTIC Science & Technology

2013-01-25

Heron triangle is an integer, then b is even, say b = 2b1. By Pythagoras ’ theorem , a4 = h2 +4b21, and since in a Heron triangle, the heights are always...our first result, which follows an idea of [10, Theorem 2.3]. Theorem 4. Let a, b be two fixed integers, and let ab be factored as in (1). Then H(a, b...which we derive the result. Theorem 4 immediately offers us an interesting observation regarding a special class of fixed sides (a, b). Corollary 5. If

Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival.

PubMed

Guan, F; Villegas, G; Teichman, J; Mundel, P; Tufro, A

2006-05-01

Class 3 semaphorins are guidance proteins that play crucial roles during development. Semaphorins 3A (sema 3A) and 3F are expressed by podocytes in vivo throughout ontogeny and their function is unknown. Here we examined the expression of class 3 semaphorins (3A, 3B, 3C, 3D, 3E, and 3F) and their receptors (neuropilins 1 and 2, plexins A1, A2, A3, B2, and D1) in undifferentiated and differentiated mouse podocytes using reverse transcriptase-polymerase chain reaction (RT-PCR). All class 3 semaphorins, neuropilins 1 and 2 are expressed by undifferentiated and differentiated podocytes at similar levels. Differentiated podocytes expressed 2-4-fold higher plexin A1, A2, and A3 mRNA levels than undifferentiated podocytes. To examine semaphorin regulation, we exposed podocytes to recombinant sema 3A. Sema 3A decreased semaphorin 3B, plexin A1, A3, and D1 >/=50% and reduced plexin A2 mRNA to undetectable levels. To identify sema 3A function in podocytes, we examined whether sema 3A regulates slit diaphragm proteins and podocyte survival. Sema 3A induced a dose-response podocin downregulation and decreased its interaction with CD2-associated protein and nephrin, as determined by Western analysis and co-immunoprecipitation. To evaluate sema 3A role in podocyte survival, we quantified podocyte apoptosis using a caspase 3 activity marker. Sema 3A induced a 10-fold increase in podocyte apoptosis and significantly decreased the activity of the Akt survival pathway. Our data indicate that (1) immortalized podocytes in culture have a functional autocrine semaphorin system that is regulated by differentiation and ligand availability; (2) sema 3A signaling regulates the expression and interactions of slit-diaphragm proteins and decreases podocyte survival.

Social Class Dialogues and the Fostering of Class Consciousness

ERIC Educational Resources Information Center

Madden, Meredith

2015-01-01

How do critical pedagogies promote undergraduate students' awareness of social class, social class identity, and social class inequalities in education? How do undergraduate students experience class consciousness-raising in the intergroup dialogue classroom? This qualitative study explores undergraduate students' class consciousness-raising in an…

Exploring patient experiences of participating in a group exercise class for the management of nonspecific shoulder pain.

PubMed

Barrett, Eva; Hayes, Amy; Kelleher, Mags; Conroy, Carmela; Robinson, Katie; O'Sullivan, Kieran; McCreesh, Karen

2018-06-01

Recent evidence has demonstrated that group-based physiotherapy interventions for musculoskeletal pain can have similar clinical outcomes compared to one-to-one treatment. This study qualitatively explored the experiences of individuals who participated in a physiotherapist-led group exercise class for people with nonspecific shoulder pain (NSSP). Semi-structured interviews were carried out with 23 people with NSSP, who had recently participated in a 6-week structured exercise class. All recorded verbal data were transcribed verbatim. Transcripts of interview data were verified by participants and analyzed using thematic analysis. The exercise class was positively evaluated by all participants. Four themes emerged from the data: (1) the participant's experiences of support, motivation, and learning from peers; (2) the preference for an exercise class compared to individual physiotherapy; (3) the physiotherapist as an educator and facilitator; and (4) beliefs about pain and exercise. Among those interviewed, the exercise class was described as providing an environment conducive to the development of relationships, friendships, humor and fun, gaining mastery of their exercises, and encouraging the transition toward self-management of their pain. For those who had previous experience of one-to-one physiotherapy, the exercise class was evaluated as the preferred mode of physiotherapy delivery. The findings of this study support a move away from traditional one-on-one physiotherapy sessions to the potentially more cost-effective group setting.

Risk-taking behaviors and subgrouping of suicide in Iran: A latent class analysis of national registries data.

PubMed

Hajebi, Ahmad; Abbasi-Ghahramanloo, Abbas; Hashemian, Seyed Sepehr; Khatibi, Seyed Reza; Ghasemzade, Masomeh; Khodadost, Mahmoud

2017-09-01

Suicide is one the most important public health problem which is rapidly growing concerns. The aim of this study was to subgroup suicide using LCA method. This cross-sectional study was conducted in Iran based on 66990 records registered in Ministry of Health in 2014. A case report questionnaire in the form of software was used for case registries. Latent class analysis was used to achieve the research objectives. Four latent classes were identified; (a) Non-lethal attempters without a history of psychiatric disorders, (b) Non-lethal attempters with a history of psychiatric disorders, (c) Lethal attempters without a history of psychiatric disorders, (d) Lethal attempters with a history of psychiatric disorders. The probability of completed/an achieved suicide is high in lethal attempter classes. Being male increases the risk of inclusion in lethal attempters' classes (OR = 4.93). Also, being single (OR = 1.16), having an age lower than 25 years (OR = 1.14) and being a rural citizen (OR = 2.36) associate with lethal attempters classes. The males tend to use more violent methods and have more completed suicide. Majority of the individuals are non-lethal attempters who need to be addressed by implementing preventive interventions and mental support provision. Copyright © 2017. Published by Elsevier B.V.

The enigma of the open cluster M29 (NGC 6913) solved

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

Straižys, V.; Milašius, K.; Černis, K.

2014-11-01

Determining the distance to the open cluster M29 (NGC 6913) has proven difficult, with distances determined by various authors differing by a factor of two or more. To solve this problem, we have initiated a new photometric investigation of the cluster in the Vilnius seven-color photometric system, supplementing it with available data in the BV and JHK {sub s} photometric systems and spectra of the nine brightest stars of spectral classes O and B. Photometric spectral classes and luminosities of 260 stars in a 15' × 15' area down to V = 19 mag are used to investigate the interstellarmore » extinction run with distance and to estimate the distance of the Great Cygnus Rift, ∼ 800 pc. The interstellar reddening law in the optical and near-infrared regions is found to be close to normal, with the ratio of extinction to color excess R{sub BV} = 2.87. The extinction A{sub V} of cluster members is between 2.5 and 3.8 mag, with a mean value of 2.97 mag, or E {sub B–V} = 1.03. The average distance of eight stars of spectral types O9-B2 is 1.54 ± 0.15 kpc. Two stars from the seven brightest stars are field stars: HDE 229238 is a background B0.5 supergiant and HD 194378 is a foreground F star. In the intrinsic color-magnitude diagram, seven fainter stars of spectral classes B3-B8 are identified as possible members of the cluster. The 15 selected members of the cluster of spectral classes O9-B8 plotted on the log L/L {sub ☉} versus log T {sub eff} diagram, together with the isochrones from the Padova database, give the age of the cluster as 5 ± 1 Myr.« less

Fingerprinting of HLA class I genes for improved selection of unrelated bone marrow donors.

PubMed

Martinelli, G; Farabegoli, P; Buzzi, M; Panzica, G; Zaccaria, A; Bandini, G; Calori, E; Testoni, N; Rosti, G; Conte, R; Remiddi, C; Salvucci, M; De Vivo, A; Tura, S

1996-02-01

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the 'fingerprinting PCR' technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heteroduplexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients' fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations.

PubMed

Liphaus, B L; Kiss, M H B; Goldberg, A C

2007-04-01

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

HLA genetic profile of Mapuche (Araucanian) Amerindians from Chile.

PubMed

Rey, Diego; Parga-Lozano, Carlos; Moscoso, Juan; Areces, Cristina; Enriquez-de-Salamanca, Mercedes; Fernández-Honrado, Mercedes; Abd-El-Fatah-Khalil, Sedeka; Alonso-Rubio, Javier; Arnaiz-Villena, Antonio

2013-07-01

Amerindian Mapuche (Araucanians) are now living in Chile and Argentina at both sides of Andean Mountains. They are anthropologically and genetically different from southernmost South America Patagonian Amerindians. Most of the HLA alleles found in our Mapuche sample are frequent or very frequent in North and South America Amerindians: (1) Class I: A*02:01, A*03:01, A*68:01, B*39:09, B*51:01, (2) Class II: DRB1*03:01, DRB1*04:03, DRB1*07:01, DRB1*08:02, DRB1*14:02, DRB1*16:02. One of the nine most frequent extended haplotypes seems to be from European origin, suggesting the existence of a degree of admixture with Europeans in our Mapuche sample. It has been calculated of about 11 % admixture. Three of the extended haplotypes are also found in other Amerindians and five of them are newly found in Mapuche Amerindians: A*68:01-B*39:09-DRB1*08:02-DQB1*04:02; A*68:01-B*51:01-DRB1*04:03-DQB1*03:02; A*29:01-B*08:01-DRB1*03:01-DQB1*02:01; A*02:01-B*15:01-DRB1*04:03-DQB1*03:02; A*33:01-B*14:02-DRB1*07:01-DQB1*03:03. The medical importance of calculating HLA profile is discussed on the diagnostic (HLA and disease) and therapeutical bases of HLA pharmacogenomics and on the construction of a virtual transplantation HLA list profile. Also, anthropological conclusions are drawn.

Termochemical Models For Slags and Silicate Melts, Review and Perspectives

NASA Astrophysics Data System (ADS)

Ottonello, G.

Thermochemical models devoted to the comprehension of reactive and mixing properties of silicate melts and slags may be roughly grouped into four main classes: 1) fictive chemical; 2) quasi chemical; 3) fictive structural; 4) polymeric. In the first class we may group the fictive regular mixture approach of Ghiorso and Carmichael [1,2]and its extensions [3-5]and the subregular model of Berman and Brown [6]. To the second class belong the modified quasi chemical approach of Pelton and coworkers [7,8] , and the Kapoor - Froberg cellular model and its extensions [9-11]. The third class has much to share with the second one (and indeed the cellular model could be ascribed to this class as well). To this class belong the "central surround model" of Sastri and Lahiri [12] , the associated solution models of Bjorkman [13], Hastie and coworkers [14]and Goel and coworkers [15], the two sublattice model of Hillert and coworkers [16]and the polynomial expansions of Hoch and Arpshofen [17] . The fourth class encompasses the models of Masson[18-20] , Toop-Samis [21,22]and its extensions [23-25] . The phylosophy beyond each one of the four classes is basically different. Benefits and drawbacks are present in any of them, and applications are often limited to simple systems (or to sufficiently complex systems, in the case of arbitrary deconvolutions of type 1) and to limited P-T ranges. The crucial aspects of the various models will be outlined to some extent. It will be shown that, often, model conflictuality is only appartent and that, in some cases, model failure is unperceived by acritical utilizers. New perspectives in the future research devoted to the comprehension of melt reactivity in compositionally complex systems, with special enphasis on the solubility of gaseous components and unmixing, will be finally discussed. References: [1] Ghiorso M.S. and Carmichael I.S.E. (1980) Contrib. Mineral. Petrol., 71, 323-342. [2] Ghiorso M.S., Carmichael I.S.E., Rivers M.L. and Sack R.O. (1983) Contrib. Mineral. Petrol., 84, 107-145. [3] Papale P. (1997) Contrib. Mineral. Petrol., 126, 237-251. [4] Papale P. (1999) Amer. Mineral., 84, 477-492. [5] Nuccio P.M. and Paonita A. (2999) Earth Planet. Sci. Letters., 183, 499-512. [6] Berman R.G. and Brown T.H. (1984) Geochim. Cosmochim. Acta, 48, 661-678. [7] Lin P.L. and Pelton A.D. (1979) Metall. Trans. B., 10B, 667-675. [8] Pelton A.D. and Blander M. (1986) Metall. Trans. B., 17B, 805-15. [9] Kapoor M.L., Mehrotre G.M. and Frohberg M.G. (1975) Proc. Aust. Inst. Mining Metall., 254, 11. [10] Kapoor M.L., Frohberg G.M. (1971) Proc. Symp. "Chemical Metallurgy of Iron and Steel" Sheffield. [11] Taylor J.R. and Dinsdale A.T. (1990] CALPHAD, 14, 71-88. [12] Sastri P. and Lahiri A.K. (1986) Metall. Trans. B., 17B, 105-110. [13] Bjorkman B. (1985) CALPHAD, 9, 271-282. [14] Hastie J.W., Horton W.S., Plante E.R. and Bonnell D.W. (1982) High Temp. High Press., 14, 669-679. [15] Goel R.P., Kellogg H.H. and Larrain J.M. (1980) Metall. Trans. B., 11B, 107-117. [16] Hillert M., Sundman B. and Wang X. (1990) Metall. Trans. B., 21B, 303-12. [17] Hoch M. and Arpshofen I. (1984) Zeits. fur Metallkde., 75, 23-29. [18] Masson C.R. (1965) Proc. Roy. Soc. London, A287, 201-221. [19] Masson C.R. (1968) J. Amer. Ceram. Soc., 51, 134-143. [20] Masson C.R. (1972) Jour. Iron Steel Inst., 210, 89-96. [21] Toop G.W. and Samis C.S. (1962) Can. Met. Quart., 1, 129-52. [22] Toop G.W. and Samis C.S. (1962) Trans. AIME, 224, 878-87. [23] Ottonello G., Moretti R., Marini L. and Vetuschi Zuccolini M. (2000) Chem. Geol., 174, 157-179. [24] Ottonello G. (2001) J. Non-Cryst. Solids, 282, 72-85. [25] Moretti R. and Ottonello G. (2002) , Metall. Trans. (submitted).

Boronic Acid Transition State Inhibitors Active against KPC and Other Class A β-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design

PubMed Central

Rojas, Laura J.; Taracila, Magdalena A.; Papp-Wallace, Krisztina M.; Bethel, Christopher R.; Caselli, Emilia; Romagnoli, Chiara; Winkler, Marisa L.; Spellberg, Brad; Prati, Fabio

2016-01-01

Boronic acid transition state inhibitors (BATSIs) are competitive, reversible β-lactamase inhibitors (BLIs). In this study, a series of BATSIs with selectively modified regions (R1, R2, and amide group) were strategically designed and tested against representative class A β-lactamases of Klebsiella pneumoniae, KPC-2 and SHV-1. Firstly, the R1 group of compounds 1a to 1c and 2a to 2e mimicked the side chain of cephalothin, whereas for compounds 3a to 3c, 4a, and 4b, the thiophene ring was replaced by a phenyl, typical of benzylpenicillin. Secondly, variations in the R2 groups which included substituted aryl side chains (compounds 1a, 1b, 1c, 3a, 3b, and 3c) and triazole groups (compounds 2a to 2e) were chosen to mimic the thiazolidine and dihydrothiazine ring of penicillins and cephalosporins, respectively. Thirdly, the amide backbone of the BATSI, which corresponds to the amide at C-6 or C-7 of β-lactams, was also changed to the following bioisosteric groups: urea (compound 3b), thiourea (compound 3c), and sulfonamide (compounds 4a and 4b). Among the compounds that inhibited KPC-2 and SHV-1 β-lactamases, nine possessed 50% inhibitory concentrations (IC50s) of ≤600 nM. The most active compounds contained the thiopheneacetyl group at R1 and for the chiral BATSIs, a carboxy- or hydroxy-substituted aryl group at R2. The most active sulfonamido derivative, compound 4b, lacked an R2 group. Compound 2b (S02030) was the most active, with acylation rates (k2/K) of 1.2 ± 0.2 × 104 M−1 s−1 for KPC-2 and 4.7 ± 0.6 × 103 M−1 s−1 for SHV-1, and demonstrated antimicrobial activity against Escherichia coli DH10B carrying blaSHV variants and blaKPC-2 or blaKPC-3 and against clinical strains of Klebsiella pneumoniae and E. coli producing different class A β-lactamase genes. At most, MICs decreased from 16 to 0.5 mg/liter. PMID:26729496

Large Observatory for X-ray Timing (LOFT-P): A Probe-Class Mission Concept Study

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen A.; Ray, P. S.; Chakrabarty, D.; Feroci, M.; Jenke, Peter; Griffith, C.; Zane, S.; Winter, B.; Brandt, S.; Hernamdez, M.;

21 CFR 864.4020 - Analyte specific reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... practitioners, e.g., forensic, academic, research, and other nonclinical laboratories. (b) Classification. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these... blood products (e.g., tests for hepatitis or tests for identifying blood groups). (c) Date of 510(k), or...

Exploring the Phenomenology of Whiteness in a Swedish Preschool Class

ERIC Educational Resources Information Center

Schwarz, Eva; Lindqvist, Beatriz

2018-01-01

This article explores how constructions of identity, race and difference permeate and are challenged in a Swedish preschool class. The study is informed by theories of phenomenology and critical whiteness. Data are drawn from a larger ethnographic study conducted in an ethnically diverse preschool. The purpose of the study was to explore how…

Characteristics of the Class of 1982

DTIC Science & Technology

1978-08-01

classification systems have you used? A. Dewey Decimal System. B. Library of Congress System. C. Both. D. Neither. 93. Have you consulted periodical...I y 4󈨒-019 UNITED V STATES, -- I ~j~1MILITARY I ~ ACADEMY WEST POINT, NEW YORK ~ J~x~ A ’ CHARACTERISTICS OF -THE CLASS OF 1982 ID DDC

7 CFR 457.107 - Florida citrus fruit crop insurance provisions.

Code of Federal Regulations, 2014 CFR

2014-01-01

...; (2) Remained on the tree after damage occurred; (3) Except as provided in (b), was missing, damaged... policies: Florida Citrus Fruit Crop Insurance Provisions 1. Definitions Age class. Trees in the unit are... applicable combination of commodity type, intended use, and age class of trees, within a citrus fruit...

14 CFR 71.71 - Class E airspace.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Class E airspace. 71.71 Section 71.71 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRSPACE... (2) The airspace below 1,500 feet above the surface of the earth. (b) The airspace areas designated...

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. TPSF manager, Martin Wilson of Jacobs Technology, holds a heated tile sample demonstrating its ability to protect a spacecraft during the heat of reentry. Looking on, from the left, are Christina Hammock, Victor Glover and Nicole Mann. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. Christina Hammock holds a tool used to mill tiles designed for use on the agency's Orion spacecraft. Also looking on are Jessica Meir, on the left, and Andrew Morgan and Tyler "Nick" Hague on the right. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. Jessica Meir, right, holds a heated tile sample demonstrating its ability to protect a spacecraft during the heat of reentry. Looking on, are Christina Hammock, left, and Anne McClain. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour the O&C with Cabana

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Operations and Checkout Building of NASA's Kennedy Space Center in Florida, astronaut candidates pose in front of a work stand where the agency's Orion spacecraft is being prepared for Exploration Flight Test EFT-1. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station. From the left are Tyler Nick Hague, Andrew Morgan, Jessica Meir, Christina Hammock, Nicole Mann, Anne McClain, Josh Cassada and Victor Glover. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on tiles being manufactured for the agency's Orion spacecraft. TPSF manager, Martin Wilson of Jacobs Technology, has just placed a tile sample in an oven to demonstrate its ability to protect a spacecraft during the heat of reentry. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on thermal blankets being manufactured for agency spacecraft. Looking at sample thermal blankets are, from the left, Nicole Mann, Andrew Morgan, Christina Hammock, Josh Cassada, Jessica Meir, Tyler ‘Nick’ Hague, and Anne McClain. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

ASCANS Class of 2013 Tour

NASA Image and Video Library

2014-03-03

CAPE CANAVERAL, Fla. -- In the Thermal Protection System Facility NASA's Kennedy Space Center in Florida, agency astronaut candidates are briefed on thermal blankets being manufactured for agency spacecraft by TPSF manager, Martin Wilson of Jacobs Technology, far left. Participating in the briefing, from the left, are Christina Hammock, Tyler ‘Nick’ Hague, Victor Glover, John Cassada, Jessica Meir, Andrew Morgan and Anne McClain. Plans call for the Lockheed Martin-built Orion to launch atop a United Launch Alliance Delta IV Heavy rocket from Cape Canaveral Air Force Station on Exploration Flight Test EFT-1 later this year. The astronaut class of 2013 was selected by NASA after an extensive year-and-a-half search. The new group will help the agency push the boundaries of exploration and travel to new destinations in the solar system. To learn more about the astronaut class of 2013, visit: http://www.nasa.gov/astronauts/2013astroclass.html Photo credit: NASA/Kim Shiflett

Antibiotic resistance genes and intI1 prevalence in a swine wastewater treatment plant and correlation with metal resistance, bacterial community and wastewater parameters.

PubMed

Yuan, Qing-Bin; Zhai, Yi-Fan; Mao, Bu-Yun; Hu, Nan

2018-06-07

The livestock wastewater treatment plant represents an important reservoir of antibiotic resistance determinants in the environment. The study explored the prevalence of five antibiotic resistance genes (ARGs, including sulI, tetA, qnrD, mphB and mcr-1) and class 1 integron (intI1) in a typical livestock wastewater treatment plant, and analyzed their integrated association with two metal resistance genes (copA and czcA), two pathogens genes (Staphylococcus and Campylobacter), bacterial community and wastewater properties. Results indicated that all investigated genes were detected in the plant. The treatment plant could not completely remove ARGs abundances, with up to 2.2 × 10 4 ~3.7 × 10 8 copies/L of them remaining in the effluent. Mcr-1 was further enriched by 27-fold in the subsequent pond. The correlation analysis showed that mphB significantly correlateed with tetA and intI. Mcr-1 strongly correlated with copA. MphB and intI significantly correlated with czcA. The correlations implied a potential co-selection risk of bacterial resistant to antibiotics and metals. Redundancy analyses indicated that qnrD and mcr-1 strongly correlated with 13 and 14 bacterial genera, respectively. Most ARGs positively correlated to wastewater nutrients, indicating that an efficient reduction of wastewater nutrients would contribute to the antibiotic resistance control. The study will provide useful implications on fates and reductions of ARGs in livestock facilities and receiving environments. Copyright © 2018. Published by Elsevier Inc.

Identifying profiles of service users in housing services and exploring their quality of life and care needs.

PubMed

Bitter, Neis A; Roeg, Diana P K; van Nieuwenhuizen, Chijs; van Weeghel, Jaap

2016-11-23

Housing services aim to support people with mental illness in their daily life and recovery. As the level of recovery differs between service users, the quality of life and care needs also might vary. However, the type and amount of care and support that service users receive do not always match their recovery. In order to improve the quality of care, this study aims to explore whether subgroups of service users exist based on three dimensions of recovery and to examine and compare the quality of life and care needs of the persons in these subgroups. Latent class analysis was performed with data from 263 service users of housing services in the Netherlands. Classes were based on three variables: personal recovery (Mental Health Recovery Measure), social recovery (Social Functioning Scale), and clinical recovery (Brief Symptom Inventory). Subsequently, the quality of life (MANSA) and care needs (CANSAS) of the different classes were analysed by the use of descriptive and inferential statistics. Three classes could be distinguished. Class 1 (45%) comprised of people who score the highest of the three classes in terms of personal and social recovery and who experience the least number of symptoms. People in class 2 (44%) and class 3 (11%) score significantly lower on personal and social recovery, and they experience significantly more symptoms compared to class 1. The distinction between class 2 and 3 can be made on the significantly higher number of symptoms in class 3. All three classes differ significantly on quality of life and unmet needs. The quality of life of service users of housing services needs improvement, as even persons in the best-recovered subgroup have a lower quality of life than the average population. Workers of housing services need to be aware of the recovery of a client and what his or her individual needs and goals are. Furthermore, better care (allocation) concerning mental and physical health and rehabilitation is needed. Care should be provided on all dimensions of recovery at the same time, therefore mental health care organisations should work together and integrate their services. ISRCTN registry ISRCTN77355880 retrospectively registered 05/07/2013.

TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues

PubMed Central

Teitell, Michael; Damore, Michael A.; Sulur, Girija G.; Turner, Devin E.; Stern, Marc-Henri; Said, Jonathan W.; Denny, Christopher T.; Wall, Randolph

1999-01-01

AIDS-related non-Hodgkin’s lymphoma (AIDS NHL) comprises a diverse and heterogeneous group of high-grade B cell tumors. Certain classes of AIDS NHL are associated with alterations in oncogenes or tumor-suppressor genes or infections by oncogenic herpesviruses. However, the clinically significant class of AIDS NHL designated immunoblastic lymphoma plasmacytoid (AIDS IBLP) lacks any consistent genetic alterations. We identified the TCL1 oncogene from a set of AIDS IBLP-associated cDNA fragments generated by subtractive hybridization with non-AIDS IBLP. Aberrant TCL1 expression has been implicated in T cell leukemia/lymphoma development, and its expression also has been seen in many established B cell tumor lines. However, TCL1 expression has not been reported in AIDS NHL. We find that TCL1 is expressed in the majority of AIDS IBLP tumors examined. TCL1 protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining. Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells, whereas follicle-center B cells (centroblasts and centrocytes) show weaker expression. These results establish TCL1 as the most prevalent of all of the surveyed oncogenes associated with AIDS IBLP. They also indicate that abundant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expression pattern of BCL-2. High-level expression in nonproliferating B cells suggests that TCL1 may function in protecting naïve preactivated B cells from apoptosis. PMID:10449776

49 CFR Appendix A to Part 238 - Schedule of Civil Penalties 1

Code of Federal Regulations, 2014 CFR

2014-10-01

....15Movement of power brake defects: (b) Improper movement from Class I or IA brake test 5,000 7,500 (c... required design features 5,000 7,500 (e) Failure to comply with hardware and software safety program 5,000... test previously used equipment 7,500 11,000 (b)(1) Failure to develop plan 7,500 11,000 (b)(2) Failure...

49 CFR Appendix A to Part 238 - Schedule of Civil Penalties 1

Code of Federal Regulations, 2010 CFR

2010-10-01

....15Movement of power brake defects: (b) Improper movement from Class I or IA brake test 5,000 7,500 (c... required design features 5,000 7,500 (e) Failure to comply with hardware and software safety program 5,000... test previously used equipment 7,500 11,000 (b)(1) Failure to develop plan 7,500 11,000 (b)(2) Failure...

Chemical Ionization Mass Spectrometry.

DTIC Science & Technology

1980-01-30

8217 ’ b o t5D&(( Irff irent from Controlling Office) IS. SECURITY CLASS. (of this report) 1< ; ~ / 1-j~. Unclassified 1S. DECLASSI FI CATION/DOWNGRADING...level in industrial sludge without any prior chromatogaphic or wet chemical separation of this comolex matrix. D. F. Hunt, J. Shabanowitz, and A. B ...Analytical Cheristry, April 1979 12)D. F. Hunt , J. Shabanowitz, and A. B . Giordani, Collision Activated Decompositions or Megative Ions in a Triple Quadrupole

75 FR 2911 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... Exchange Act of 1934 (the ``Act''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January... proposed rule change from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. \\3\\ 15 U.S.C... Effectiveness of Proposed Rule Change To Permit Concurrent Listing of $3.50 and $4 Strikes for Classes in the $0...

Identity processes and personality traits and types in adolescence: directionality of effects and developmental trajectories.

PubMed

Luyckx, Koen; Teppers, Eveline; Klimstra, Theo A; Rassart, Jessica

2014-08-01

Personality traits are hypothesized to be among the most important factors contributing to individual differences in identity development. However, longitudinal studies linking Big Five personality traits to contemporary identity models (in which multiple exploration and commitment processes are distinguished) are largely lacking. To gain more insight in the directionality of effect and the developmental interdependence of the Big Five and identity processes as forwarded in multilayered personality models, the present study assessed personality and identity in 1,037 adolescents 4 times over a period of 3 years. First, using cross-lagged path analysis, Big Five traits emerged as consistent predictors of identity exploration processes, whereas only one significant path from identity exploration to the Big Five was found. Second, using latent class growth analysis, 3 Big Five trajectory classes were identified, resembling the distinctions typically made between resilients, overcontrollers, and undercontrollers. These classes were characterized by different initial levels and (to a lesser extent) rates of change in commitment and exploration processes. In sum, important developmental associations linking personality traits to identity processes were uncovered, emphasizing the potential role of personality traits in identity development. Developmental implications and suggestions for future research are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Lepton-flavor universality limits in warped space

NASA Astrophysics Data System (ADS)

Megías, Eugenio; Quirós, Mariano; Salas, Lindber

2017-10-01

We explore the limits on lepton-flavor universality (LFU) violation in theories where the hierarchy problem is solved by means of a warped extra dimension. In those theories, LFU violation, in fermion interaction with Kaluza-Klein modes of gauge bosons, is provided ab initio when different flavors of fermions are differently localized along the extra dimension. As this fact arises from the mass pattern of quarks and leptons, LFU violation is natural in this class of theories. We analyze the experimental data pointing toward LFU violation, as well as the most relevant electroweak and flavor observables, and the LFU tests in the μ /e and τ /μ sectors. We find agreement with RK(*) and RD(*) data at 95% C.L., provided the third-generation left-handed fermions are composite (0.14

Atrial Fibrillation During an Exploration Class Mission

NASA Technical Reports Server (NTRS)

Lipset, Mark A.; Lemery, Jay; Polk, J. D.; Hamilton, Douglas R.

2010-01-01

Background: A long-duration exploration class mission is fraught with numerous medical contingency plans. Herein, we explore the challenges of symptomatic atrial fibrillation (AF) occurring during an exploration class mission. The actions and resources required to ameliorate the situation, including the availability of appropriate pharmaceuticals, monitoring devices, treatment modalities, and communication protocols will be investigated. Challenges of Atrial Fibrillation during an Exploration Mission: Numerous etiologies are responsible for the initiation of AF. On Earth, we have the time and medical resources to evaluate and determine the causative situation for most cases of AF and initiate therapy accordingly. During a long-duration exploration class mission resources will be severely restricted. How is one to determine if new onset AF is due to recent myocardial infarction, pulmonary embolism, fluid overload, thyrotoxicosis, cardiac structural abnormalities, or CO poisoning? Which pharmaceutical therapy should be initiated and what potential side effects can be expected? Should anti-coagulation therapy be initiated? How would one monitor the therapeutic treatment of AF in microgravity? What training would medical officers require, and which communication strategies should be developed to enable the best, safest therapeutic options for treatment of AF during a long-duration exploration class mission? Summary: These questions will be investigated with expert opinion on disease elucidation, efficient pharmacology, therapeutic monitoring, telecommunication strategies, and mission cost parameters with emphasis on atrial fibrillation being just one illustration of the tremendous challenges that face a long-duration exploration mission. The limited crew training time, medical hardware, and drugs manifested to deal with such an event predicate that aggressive primary and secondary prevention strategies be developed to protect a multibillion-dollar asset like the International Space Station or a mission to the Moon or Mars. Learning Objectives: The audience will become familiar with the risks and challenges inherent to developing a therapeutic strategy for the treatment of atrial fibrillation during a long-term exploration class mission.

26 CFR 1.922-1 - Requirements that a corporation must satisfy to be a FSC or a small FSC.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the Caribbean Basin Economic Recovery Act (Code section 274(h)((6)(C)), or (B) a bilateral income tax... counted as a shareholder. (g) Class of stock. Q-7. What is preferred stock for purposes of determining... liquidation. Q-8. Can a corporation have outstanding more than one class of common stock? A-8. Yes. However...

Exploring Latent Class Based on Growth Rates in Number Sense Ability

ERIC Educational Resources Information Center

Kim, Dongil; Shin, Jaehyun; Lee, Kijyung

2013-01-01

The purpose of this study was to explore latent class based on growth rates in number sense ability by using latent growth class modeling (LGCM). LGCM is one of the noteworthy methods for identifying growth patterns of the progress monitoring within the response to intervention framework in that it enables us to analyze latent sub-groups based not…

Exploring Communication and Course Format: Conversation Frequency and Duration, Student Motives, and Perceived Teacher Approachability for Out-of-Class Contact

ERIC Educational Resources Information Center

Brooks, Catherine F.; Young, Stacy L.

2016-01-01

This study explored how course instructional format (i.e., online, face-to-face, or hybrid) is related to the frequency and duration of out-of-class communication (OCC) between college instructors and students, to student motives for communicating with teachers, and to perceived teacher approachability for conversation outside of class. Though…

Exploring the Impact of a Standards-Based Mathematics and Pedagogy Class on Preservice Teachers' Beliefs and Subject Matter Knowledge

ERIC Educational Resources Information Center

Stohlmann, Micah Stephen

2012-01-01

This case study explored the impact of a standards-based mathematics and pedagogy class on preservice elementary teachers' beliefs and conceptual subject matter knowledge of linear functions. The framework for the standards-based mathematics and pedagogy class in this study involved the National Council of Teachers of Mathematics Standards,…

Exploring Feminism in a Multicultural Classroom: Using "Bend It Like Beckham" as a Tool in a High School Class

ERIC Educational Resources Information Center

Thomas, Paul; Røthing, Åse

2017-01-01

This study concerns itself with a classroom project in English class where the film "Bend it Like Beckham" was shown to two multicultural classes in a high school in Oslo, Norway, with a view towards exploring students' understandings and attitudes towards gender. Using an ethnographic methodology informed by feminist approaches,…

Smart in Mathematics? Exploring the Effects of In-Class-Level Differentiation Using SMARTboard on Math Proficiency

ERIC Educational Resources Information Center

Cabus, Sofie J.; Haelermans, Carla; Franken, Sonja

2017-01-01

This paper explored the effects of in-class-level differentiation by making innovative use of an interactive whiteboard (SMARTboard) on math proficiency. Therefore, this paper evaluates the use of SMARTboard in class, in combination with teacher training, using a randomized field experiment among 199 pre-vocational students in seventh grade in the…

Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase

PubMed Central

Lin, Mingqun; Liu, Hongyan; Xiong, Qingming; Niu, Hua; Cheng, Zhihui; Yamamoto, Akitsugu; Rikihisa, Yasuko

2016-01-01

Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5). Ehrlichia acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer. Moreover, ATG5 and RAB5A/B/C were routed to ehrlichial inclusions. RAB5A/B/C siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection. Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions. Ectopically expressed Etf-1 activated class III PtdIns3K as in E. chaffeensis infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation. These data support the notion that E. chaffeensis secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing. PMID:27541856