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Sample records for non-selective conductance unrelated

  1. [Hyperprolactinemia unrelated to prolactinoma].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2014-01-01

    Hyperprolactinemia, defined as prolactin levels above the upper limit of normal range, is the most frequent hypothalamus-pituitary dysfunction. Clinical symptoms of hyperprolactinemia in women include oligomenorrhea, infertility, and galactorrhea, while in men the condition may lead to hypogonadism, decreased libido, erectile dysfunction, infertility, gynecomastia, and, in rare instances, galactorrhea. In many patients, hyperprolactinemia results from the presence of prolactinoma, which is considered as the most common hormone-secreting pituitary tumors. However, transient or long-term hyperprolactinemia may also develop during different physiological situations or due to several diseases. It is also a frequent but often neglected side effect of many drugs, particularly of antipsychotics. Finally, hyperprolactinemia may be secondary to the predominance of high molecular mass circulating prolactin forms that have been postulated to represent complexes of prolactin and anti-prolactin immunoglobulins (macroprolactinemia). The cause of hyperprolactinemia determines its treatment. In this paper, we review the causes of hyperprolactinemia unrelated to prolactinoma, providing a differential diagnosis of this condition.

  2. Non-Selective Evolution of Growing Populations

    PubMed Central

    Jung, Heinrich; Frey, Erwin

    2015-01-01

    Non-selective effects, like genetic drift, are an important factor in modern conceptions of evolution, and have been extensively studied for constant population sizes (Kimura, 1955; Otto and Whitlock, 1997). Here, we consider non-selective evolution in the case of growing populations that are of small size and have varying trait compositions (e.g. after a population bottleneck). We find that, in these conditions, populations never fixate to a trait, but tend to a random limit composition, and that the distribution of compositions “freezes” to a steady state. This final state is crucially influenced by the initial conditions. We obtain these findings from a combined theoretical and experimental approach, using multiple mixed subpopulations of two Pseudomonas putida strains in non-selective growth conditions (Matthijs et al, 2009) as model system. The experimental results for the population dynamics match the theoretical predictions based on the Pólya urn model (Eggenberger and Pólya, 1923) for all analyzed parameter regimes. In summary, we show that exponential growth stops genetic drift. This result contrasts with previous theoretical analyses of non-selective evolution (e.g. genetic drift), which investigated how traits spread and eventually take over populations (fixate) (Kimura, 1955; Otto and Whitlock, 1997). Moreover, our work highlights how deeply growth influences non-selective evolution, and how it plays a key role in maintaining genetic variability. Consequently, it is of particular importance in life-cycles models (Melbinger et al, 2010; Cremer et al, 2011; Cremer et al, 2012) of periodically shrinking and expanding populations. PMID:26274606

  3. Unrelated business income tax: an update.

    PubMed

    Fama, A J

    1984-02-01

    To meet spiraling costs, tax-exempt hospitals increasingly are operating businesses unrelated to direct patient care. Knowing which activities may be open to challenge by the Internal Revenue Service (IRS) is essential to avoid the unrelated business income (UBI) tax. Three criteria must be met for an activity to be taxable as UBI: It must constitute a trade or business; It must be regularly carried on; and It must be unrelated to the organization's exempt purpose. The Internal Revenue Code and IRS rulings clearly exclude the following areas from UBI taxation: Activities performed by unpaid volunteers (e.g., hospital auxiliaries' fund-raising dinners and bazaars and the operation of thrift stores); Operations conducted for the convenience of the organization's members, students, patients, or employees (e.g., gift shops, cafeterias, coffee shops, parking lots, lounges, vending machines, pharmaceutical sales to inpatients and emergency room outpatients, and research activities for students' benefit; The sale of merchandise that has been received by gift (e.g., flea markets, baked goods sales, book sales, and rummage sales); Investment income such as dividends, interest, annuities, royalties, certain rents, and capital gains from the sale of investment assets; Gifts or contributions made directly to the facility; and Bingo games that are conducted commercially. Areas which may be subject to UBI taxation, or in which there have been controversial or contradictory court rulings, include: Pharmaceutical sales to the public or private physicians' patients; and Laboratory services provided to private physicians for treating their patients. IRS private letter rulings, though not precedential, have excluded from UBI taxation the x-ray income from a hospital's branch facility and rental income from property leased for use as a clinic or medical office building that is substantially related to the hospital's exempt functions. Private letter rulings have subjected to UBI

  4. 26 CFR 1.513-5 - Certain bingo games not unrelated trade or business.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Certain bingo games not unrelated trade or... Organizations § 1.513-5 Certain bingo games not unrelated trade or business. (a) In general. Under section 513(f... or business that consists of conducting bingo games (as defined in paragraph (d) of this section)....

  5. 26 CFR 1.513-5 - Certain bingo games not unrelated trade or business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Certain bingo games not unrelated trade or... Organizations § 1.513-5 Certain bingo games not unrelated trade or business. (a) In general. Under section 513(f... or business that consists of conducting bingo games (as defined in paragraph (d) of this section)....

  6. 26 CFR 1.513-5 - Certain bingo games not unrelated trade or business.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Certain bingo games not unrelated trade or... Organizations § 1.513-5 Certain bingo games not unrelated trade or business. (a) In general. Under section 513(f... or business that consists of conducting bingo games (as defined in paragraph (d) of this section)....

  7. 26 CFR 1.513-5 - Certain bingo games not unrelated trade or business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Certain bingo games not unrelated trade or... Organizations § 1.513-5 Certain bingo games not unrelated trade or business. (a) In general. Under section 513(f... or business that consists of conducting bingo games (as defined in paragraph (d) of this section)....

  8. 26 CFR 1.513-5 - Certain bingo games not unrelated trade or business.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Certain bingo games not unrelated trade or... Organizations § 1.513-5 Certain bingo games not unrelated trade or business. (a) In general. Under section 513(f... or business that consists of conducting bingo games (as defined in paragraph (d) of this section)....

  9. Exemptions from Unrelated Business Tax: Rental Income

    ERIC Educational Resources Information Center

    Reed, George E.

    1975-01-01

    Section 512(b) of the Internal Revenue Code contains several categorical exemptions from the unrelated business tax including rental income. The article covers various problems faced by nonprofit organizations such as parochial schools in leasing or selling property. (LBH)

  10. On Non-Selective Harvesting of a Multispecies Fishery

    ERIC Educational Resources Information Center

    Kar, Tapan Kuman; Chaudhuri, K. S.

    2002-01-01

    The present paper deals with the problem of non-selective harvesting of a prey-predator system in which both the prey and the predator species obey the law of logistic growth and each predators functional response to the prey approaches a constant as the prey population increases. Boundedness of the exploited system is examined. The existence of…

  11. Non-Selective Lexical Access in Different-Script Bilinguals

    ERIC Educational Resources Information Center

    Moon, Jihye; Jiang, Nan

    2012-01-01

    Lexical access in bilinguals is known to be largely non-selective. However, most studies in this area have involved bilinguals whose two languages share the same script. This study aimed to examine bilingual lexical access among bilinguals whose two languages have distinct scripts. Korean-English bilinguals were tested in a phoneme monitoring task…

  12. Non-selective cation channels in plasma and vacuolar membranes and their contribution to K+ transport.

    PubMed

    Pottosin, Igor; Dobrovinskaya, Oxana

    2014-05-15

    Both in vacuolar and plasma membranes, in addition to truly K(+)-selective channels there is a variety of non-selective channels, which conduct K(+) and other ions with little preference. Many non-selective channels in the plasma membrane are active at depolarized potentials, thus, contributing to K(+) efflux rather than to K(+) uptake. They may play important roles in xylem loading or contribute to a K(+) leak, induced by salt or oxidative stress. Here, three currents, expressed in root cells, are considered: voltage-insensitive cation current, non-selective outwardly rectifying current, and low-selective conductance, activated by reactive oxygen species. The latter two do not only poorly discriminate between different cations (like K(+)vs Na(+)), but also conduct anions. Such solute channels may mediate massive electroneutral transport of salts and might be involved in osmotic adjustment or volume decrease, associated with cell death. In the tonoplast two major currents are mediated by SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually impermeable for anions. SV channels conduct mono- and divalent cations indiscriminately and are activated by high cytosolic Ca(2+) and depolarized voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and polyamines, and conduct a variety of monovalent cations, including K(+). Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which modulates their voltage dependence, and in case of SV, also alleviates channel's inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)-sensing valves, controlling K(+) distribution between the vacuole and the cytosol.

  13. New PHA products using unrelated carbon sources

    PubMed Central

    Matias, Fernanda; de Andrade Rodrigues, Maria Filomena

    2011-01-01

    Polyhydroxyalkanoates (PHA) are natural polyesters stored by a wide range of bacteria as carbon source reserve. Due to its chemical characteristics and biodegradability PHA can be used in chemical, medical and pharmaceutical industry for many human purposes. Over the past years, few Burkholderia species have become known for production of PHA. Aside from that, these bacteria seem to be interesting for discovering new PHA compositions which is important to different industrial applications. In this paper, we introduce two new strains which belong either to Burkholderia cepacia complex (Bcc) or genomovar-type, Burkholderia cepacia SA3J and Burkholderia contaminans I29B, both PHA producers from unrelated carbon sources. The classification was based on 16S rDNA and recA partial sequence genes and cell wall fatty acids composition. These two strains were capable to produce different types of PHA monomers or precursors. Unrelated carbon sources were used for growth and PHA accumulation. The amount of carbon source evaluated, or mixtures of them, was increased with every new experiment until it reaches eighteen carbon sources. As first bioprospection experiments staining methods were used with colony fluorescent dye Nile Red and the cell fluorescent dye Nile Blue A. Gas chromatography analysis coupled to mass spectrometry was used to evaluate the PHA composition on each strain cultivated on different carbon sources. The synthesized polymers were composed by short chain length-PHA (scl-PHA), especially polyhydroxybutyrate, and medium chain length-PHA (mcl-PHA) depending on the carbon source used. PMID:24031764

  14. Globally, unrelated protein sequences appear random

    PubMed Central

    Lavelle, Daniel T.; Pearson, William R.

    2010-01-01

    Motivation: To test whether protein folding constraints and secondary structure sequence preferences significantly reduce the space of amino acid words in proteins, we compared the frequencies of four- and five-amino acid word clumps (independent words) in proteins to the frequencies predicted by four random sequence models. Results: While the human proteome has many overrepresented word clumps, these words come from large protein families with biased compositions (e.g. Zn-fingers). In contrast, in a non-redundant sample of Pfam-AB, only 1% of four-amino acid word clumps (4.7% of 5mer words) are 2-fold overrepresented compared with our simplest random model [MC(0)], and 0.1% (4mers) to 0.5% (5mers) are 2-fold overrepresented compared with a window-shuffled random model. Using a false discovery rate q-value analysis, the number of exceptional four- or five-letter words in real proteins is similar to the number found when comparing words from one random model to another. Consensus overrepresented words are not enriched in conserved regions of proteins, but four-letter words are enriched 1.18- to 1.56-fold in α-helical secondary structures (but not β-strands). Five-residue consensus exceptional words are enriched for α-helix 1.43- to 1.61-fold. Protein word preferences in regular secondary structure do not appear to significantly restrict the use of sequence words in unrelated proteins, although the consensus exceptional words have a secondary structure bias for α-helix. Globally, words in protein sequences appear to be under very few constraints; for the most part, they appear to be random. Contact: wrp@virginia.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19948773

  15. PedMine – A simulated annealing algorithm to identify maximally unrelated individuals in population isolates

    PubMed Central

    Douglas, Julie A.; Sandefur, Conner I.

    2010-01-01

    Summary In family-based genetic studies, it is often useful to identify a subset of unrelated individuals. When such studies are conducted in population isolates, however, most if not all individuals are often detectably related to each other. To identify a set of maximally unrelated (or equivalently, minimally related) individuals, we have implemented simulated annealing, a general-purpose algorithm for solving difficult combinatorial optimization problems. We illustrate our method on data from a genetic study in the Old Order Amish of Lancaster County, Pennsylvania, a population isolate derived from a modest number of founders. Given one or more pedigrees, our program automatically and rapidly extracts a fixed number of maximally unrelated individuals. PMID:18321883

  16. Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes.

    PubMed

    Nardid, Oleg A; Schetinskey, Miroslav I; Kucherenko, Yuliya V

    2013-03-01

    Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used in biological research, cryobiology and medicine. On cellular level DMSO was shown to suppress NMDA-AMPA channels activation, blocks Na+ channel activation and attenuates Ca2+ influx (Lu and Mattson 2001). In the present study we explored the whole-cell patch-clamp to examine the acute effect of high concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl--containing saline buffer solution significantly inhibited cation conductance in human erythrocytes. Inhibition was concentration-dependent and had an exponential decay profile. DMSO (2 mol/l) induced cation inhibition in Cl-- containing saline solutions of: 40.3 ± 3.9% for K+, 35.4 ± 3.1% for Ca2+ and 47.4 ± 1.9% for NMDG+. Substitution of Cl- with gluconate- increased the inhibitory effect of DMSO on the Na+ current. Inhibitory effect of DMSO was neither due to high permeability of erythrocytes to DMSO nor to an increased tonicity of the bath media since no effect was observed in 2 mol/l glycerol solution. In conclusion, we have shown that high concentrations of DMSO inhibit the non-selective cation channels in human erythrocytes and thus protect the cells against Na+ and Ca2+ overload. Possible mechanisms of DMSO effect on cation conductance are discussed. PMID:23531832

  17. Do people remember the temporal proximity of unrelated events?

    PubMed

    Friedman, William J; Janssen, Steve M J

    2010-12-01

    In the present study, we tested the ability to remember the temporal proximity of two unrelated events that had happened within 7 days of one another. In three experiments, 1,909 participants judged whether pairs of news events, ranging in age from 1 month to about 6 years, had occurred within a week of each other and, if not, how far apart they had occurred. Some event pairs were related, and others were unrelated. For unrelated event pairs, same-week and separation judgments were very poor. Accuracy was much greater for both kinds of judgments when the events were related. Participants often guessed the separation of unrelated event pairs, whereas they frequently deduced the separation or remembered the proximity of related event pairs. For both types of pairs, the participants reported using the strength of the memories or the general period in which the events had occurred.

  18. Effect of non-selective dopaminergic receptor agonist on disrupted maternal behavior in olfactory bulbectomized mice.

    PubMed

    Sato, Atsushi; Nakagawasai, Osamu; Tan-No, Koichi; Onogi, Hiroshi; Niijima, Fukie; Tadano, Takeshi

    2010-07-11

    Olfactory bulbectomy (OBX) animals are considered a putative model of depression that produces behavioral, physiological, and neurochemical alterations resembling clinical depression. Depression is a critical cause of child abuse and neglect, and it has been reported that maternal behavior involves dopaminergic neurons of the mesolimbic pathway. In this study, we investigated the effect of apomorphine, a non-selective dopaminergic receptor agonist, on maternal behavior to examine the influence of activated brain dopaminergic function in OBX mice. In addition, we conducted the sucrose preference test to examine the reward system which has a critical relationship to mesolimbic dopaminergic function and maternal behavior. Maternal behavior was observed on postnatal day (PND) 0 and 4. OBX female mice showed a reduction in sucrose preference 2 weeks post surgery. OBX dams showed maternal behavior deficits on PND 0, and these deficits were ameliorated by administration of apomorphine. These results suggest that maternal behavior deficits in OBX dams may involve brain hypodopaminergic function in the central nervous system induced by OBX. PMID:20219556

  19. Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle.

    PubMed

    Zhang, Ting; Luo, Xiao-Jing; Sai, Wen-Bo; Yu, Meng-Fei; Li, Wen-Er; Ma, Yun-Fei; Chen, Weiwei; Zhai, Kui; Qin, Gangjian; Guo, Donglin; Zheng, Yun-Min; Wang, Yong-Xiao; Shen, Jin-Hua; Ji, Guangju; Liu, Qing-Hua

    2014-01-01

    Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.

  20. Unrelated Future Costs and Unrelated Future Benefits: Reflections on NICE Guide to the Methods of Technology Appraisal.

    PubMed

    Morton, Alec; Adler, Amanda I; Bell, David; Briggs, Andrew; Brouwer, Werner; Claxton, Karl; Craig, Neil; Fischer, Alastair; McGregor, Peter; van Baal, Pieter

    2016-08-01

    In this editorial, we consider the vexing issue of 'unrelated future costs' (for example, the costs of caring for people with dementia or kidney failure after preventing their deaths from a heart attack). The National Institute of Health and Care Excellence (NICE) guidance is not to take such costs into account in technology appraisals. However, standard appraisal practice involves modelling the benefits of those unrelated technologies. We argue that there is a sound principled reason for including both the costs and benefits of unrelated care. Changing this practice would have material consequences for decisions about reimbursing particular technologies, and we urge future research to understand this better. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27374115

  1. The Recognition of Identical Ligands by Unrelated Proteins.

    PubMed

    Barelier, Sarah; Sterling, Teague; O'Meara, Matthew J; Shoichet, Brian K

    2015-12-18

    The binding of drugs and reagents to off-targets is well-known. Whereas many off-targets are related to the primary target by sequence and fold, many ligands bind to unrelated pairs of proteins, and these are harder to anticipate. If the binding site in the off-target can be related to that of the primary target, this challenge resolves into aligning the two pockets. However, other cases are possible: the ligand might interact with entirely different residues and environments in the off-target, or wholly different ligand atoms may be implicated in the two complexes. To investigate these scenarios at atomic resolution, the structures of 59 ligands in 116 complexes (62 pairs in total), where the protein pairs were unrelated by fold but bound an identical ligand, were examined. In almost half of the pairs, the ligand interacted with unrelated residues in the two proteins (29 pairs), and in 14 of the pairs wholly different ligand moieties were implicated in each complex. Even in those 19 pairs of complexes that presented similar environments to the ligand, ligand superposition rarely resulted in the overlap of related residues. There appears to be no single pattern-matching "code" for identifying binding sites in unrelated proteins that bind identical ligands, though modeling suggests that there might be a limited number of different patterns that suffice to recognize different ligand functional groups.

  2. 20 CFR 220.103 - Two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Two or more unrelated impairments-initial... RAILROAD RETIREMENT ACT DETERMINING DISABILITY Evaluation of Disability § 220.103 Two or more unrelated impairments—initial claims. (a) Unrelated severe impairments. Two or more unrelated severe impairments...

  3. 20 CFR 416.922 - When you have two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false When you have two or more unrelated... of Disability § 416.922 When you have two or more unrelated impairments—initial claims. (a) Unrelated severe impairments. We cannot combine two or more unrelated severe impairments to meet the...

  4. Brightness perception of unrelated self-luminous colors.

    PubMed

    Withouck, Martijn; Smet, Kevin A G; Ryckaert, Wouter R; Pointer, Michael R; Deconinck, Geert; Koenderink, Jan; Hanselaer, Peter

    2013-06-01

    The perception of brightness of unrelated self-luminous colored stimuli of the same luminance has been investigated. The Helmholtz-Kohlrausch (H-K) effect, i.e., an increase in brightness perception due to an increase in saturation, is clearly observed. This brightness perception is compared with the calculated brightness according to six existing vision models, color appearance models, and models based on the concept of equivalent luminance. Although these models included the H-K effect and half of them were developed to work with unrelated colors, none of the models seemed to be able to fully predict the perceived brightness. A tentative solution to increase the prediction accuracy of the color appearance model CAM97u, developed by Hunt, is presented.

  5. Renal impairment in cirrhosis unrelated to hepatorenal syndrome

    PubMed Central

    Low, Gavin; Alexander, Graeme JM; Lomas, David J

    2015-01-01

    Renal impairment is common in liver disease and may occur as a consequence of the pathophysiological changes that underpin cirrhosis or secondary to a pre-existing unrelated insult. Nevertheless, the onset of renal impairment often portends a worsening prognosis. Hepatorenal syndrome remains one of the most recognized and reported causes of renal impairment in cirrhosis. However, other causes of renal impairment occur and can be classified into prerenal, intrinsic or postrenal, which are the subjects of the present review. PMID:25874649

  6. Clinical Impact of Selective and Non-selective Beta Blockers on Survival in Ovarian Cancer Patients

    PubMed Central

    Watkins, Jack L.; Thaker, Premal H.; Nick, Alpa M.; Ramondetta, Lois M.; Kumar, Sanjeev; Urbauer, Diana L.; Matsuo, Koji; Squires, Kathryn; Lutgendorf, Susan K.; Ramirez, Pedro T.; Sood, Anil K.

    2015-01-01

    BACKGROUND Preclinical evidence suggests that sustained adrenergic activation can promote ovarian cancer growth and metastasis. We examined the impact of beta-adrenergic blockade on clinical outcome of women with epithelial ovarian, primary peritoneal or fallopian tube cancers (collectively, EOC). METHODS A multicenter review of 1,425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta blocker use during chemotherapy and those without beta blocker use. RESULTS The median age of patients in this study was 63 years (range, 21–93 years). The sample included 269 patients who received beta blockers. Of those, 193 (71.7%) were receiving beta-1 adrenergic receptor (ADRB1) selective agents, and the remaining patients were receiving non-selective beta antagonists. The primary indication for beta blocker use was hypertension but also included arrhythmia and post-myocardial infarction management. For patients receiving any beta blocker, the median overall survival (OS) was 47.8 months versus42 months (P = 0.04) for non-users. The median OS based on beta blocker receptor selectivity was 94.9 months for those receiving non-selective beta blockers versus 38 months for those receiving ADRB1 selective agents (P < 0.001). Hypertension was associated with decreased OS compared to no hypertension across all groups. However, even in patients with hypertension, users of a non-selective beta blocker had a longer median OS than non-users observed (38.2 vs 90 months, P < 0.001). CONCLUSION Use of non-selective beta blockers in epithelial ovarian cancer patients was associated with longer OS. These findings may have implications for new therapeutic approaches. PMID:26301456

  7. Selective and non-selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna.

    PubMed

    Kidd, Lisa J; Cowling, Nick R; Wu, Andy C; Kelly, Wendy L; Forwood, Mark R

    2013-02-01

    Anti-inflammatory drugs are widely used to manage pain associated with stress fractures (SFxs), but little is known about their effects on healing of those injuries. We hypothesized that selective and non-selective anti-inflammatory treatments would retard the healing of SFx in the rat ulna. SFxs were created by cyclic loading of the ulna in Wistar rats. Ulnae were harvested 2, 4 or 6 weeks following loading. Rats were treated with non-selective NSAID, ibuprofen (30 mg/kg/day); selective COX-2 inhibition, [5,5-dimethyl-3-3 (3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone] (DFU) (2.0 mg/kg/day); or the novel c5a anatagonist PMX53 (10 mg/kg/day, 4 and 6 weeks only); with appropriate vehicle as control. Quantitative histomorphometric measurements of SFx healing were undertaken. Treatment with the selective COX-2 inhibitor, DFU, reduced the area of resorption along the fracture line at 2 weeks, without affecting bone formation at later stages. Treatment with the non-selective, NSAID, ibuprofen decreased both bone resorption and bone formation so that there was significantly reduced length and area of remodeling and lamellar bone formation within the remodeling unit at 6 weeks after fracture. The C5a receptor antagonist PMX53 had no effect on SFx healing at 4 or 6 weeks after loading, suggesting that PMX53 would not delay SFx healing. Both selective COX-2 inhibitors and non-selective NSAIDs have the potential to compromise SFx healing, and should be used with caution when SFx is diagnosed or suspected. PMID:22847634

  8. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    PubMed

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7838348

  9. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    PubMed

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression.

    PubMed

    Hans, Gregory; Wislet-Gendebien, Sabine; Lallemend, François; Robe, Pierre; Rogister, Bernard; Belachew, Shibeshih; Nguyen, Laurent; Malgrange, Brigitte; Moonen, Gustave; Rigo, Jean-Michel

    2005-03-01

    Some synthetic ligands of the peripheral-type benzodiazepine receptor (PBR), an 18 kDa protein of the outer mitochondrial membrane, are cytotoxic for several tumor cell lines and arise as promising chemotherapeutic candidates. However, conflicting results were reported regarding the actual effect of these drugs on cellular survival ranging from protection to toxicity. Moreover, the concentrations needed to observe such a toxicity were usually high, far above the affinity range for their receptor, hence questioning its specificity. In the present study, we have shown that micromolar concentrations of FGIN-1-27 and Ro 5-4864, two chemically unrelated PBR ligands are toxic for both PBR-expressing SK-N-BE neuroblastoma cells and PBR-deficient Jurkat lymphoma cells. We have thereby demonstrated that the cytotoxicity of these drugs is unrelated to their PBR-binding activity. Moreover, Ro 5-4864-induced cell death differed strikingly between both cell types, being apoptotic in Jurkat cells while necrotic in SK-N-BE cells. Again, this did not seem to be related to PBR expression since Ro 5-4864-induced death of PBR-transfected Jurkat cells remained apoptotic. Taken together, our results show that PBR is unlikely to mediate all the effects of these PBR ligands. They however confirm that some of these ligands are very effective cytotoxic drugs towards various cancer cells, even for reputed chemoresistant tumors such as neuroblastoma, and, surprisingly, also for PBR-lacking tumor cells.

  11. Tailoring compensation effects of health-unrelated food properties.

    PubMed

    Mai, Robert; Zahn, Susann; Hoppert, Karin; Hoffmann, Stefan; Rohm, Harald

    2014-09-01

    With the steady rise of the adiposity epidemic, there are increasing calls to stimulate healthier food choices. This is difficult, however, because consumers hold the nearly universal belief that healthy foods are less tasty. To increase their attractiveness, optimizing certain health-unrelated food attributes may help compensate for the loss in taste that is caused by the reduction of fat or sugar. The overall objective of this paper is to examine the boundary conditions under which such compensation effects emerge. Using the example of cookies, we examine how compensation effects depend on (i) the consumer segment, (ii) the configuration of the food product, and (iii) the type of evaluation process. This paper empirically tests compensation effects for optimized flavor intensity. We apply a combination of adaptive conjoint analysis and sensory preference tests. Market simulations and sensitivity analyses demonstrate that the intricate interplay among the three contingency variables is far more important than the question of whether compensation effects emerge or not. The analyses uncover four distinct segments and they show that compensation effects depend on which type of health-related attribute is reduced and whether the health-unrelated attribute is improved intrinsically or extrinsically.

  12. Thiram and ziram stimulate non-selective cation channel and induce apoptosis in PC12 cells.

    PubMed

    Sook Han, Myoung; Shin, Kum Joo; Kim, Yun Hee; Kim, Sun Hee; Lee, Taehoon; Kim, Euikyung; Ho Ryu, Sung; Suh, Pann Ghill

    2003-06-01

    The neurotoxicity of dithiocarbamates has been previously reported, however, the detailed mechanism underlying the neurotoxicity is still not fully understood. Among the dithiocarbamates, we investigated thiram and ziram in a neuronal-like pheochromocytoma (PC12) cells. Thiram and ziram strongly induced cell death in both dose- and time-dependent manners with the LC(50) of 0.3 and 2 microM, respectively. The cell death showed typical apoptotic features, such as DNA fragmentation and an increase of subdiploidy nuclei. Interestingly, both thiram and ziram induced rapid and sustained increases of intracellular Ca(2+) in PC12 cells, which were almost completely blocked by flufenamic acid (FFA), an inhibitor of non-selective cation channel. BAPTA-AM, an intracellular Ca(2+) chelator, inhibited the thiram- and ziram-induced apoptotic cell death. These results suggest that thiram and ziram induce apoptotic neuronal cell death by Ca(2+) influx through non-selective cation channels. The present study may provide a clue for understanding the mechanism of neurotoxicity of thiram and ziram.

  13. Minimum viable population sizes and global extinction risk are unrelated.

    PubMed

    Brook, Barry W; Traill, Lochran W; Bradshaw, Corey J A

    2006-04-01

    Theoretical and empirical work has shown that once reduced in size and geographical range, species face a considerably elevated risk of extinction. We predict minimum viable population sizes (MVP) for 1198 species based on long-term time-series data and model-averaged population dynamics simulations. The median MVP estimate was 1377 individuals (90% probability of persistence over 100 years) but the overall distribution was wide and strongly positively skewed. Factors commonly cited as correlating with extinction risk failed to predict MVP but were able to predict successfully the probability of World Conservation Union Listing. MVPs were most strongly related to local environmental variation rather than a species' intrinsic ecological and life history attributes. Further, the large variation in MVP across species is unrelated to (or at least dwarfed by) the anthropogenic threats that drive the global biodiversity crisis by causing once-abundant species to decline.

  14. Repeated text in unrelated passages: Repetition versus meaning selection effects.

    PubMed

    Klin, Celia M; Drumm, April M; Ralano, Angela S

    2009-07-01

    Despite previous findings, Klin, Ralano, and Weingartner (2007) found transfer benefits across unrelated passages. After processing an ambiguous phrase in Story A that was biased toward its sarcastic meaning, readers were more likely to interpret the identical phrase in Story B as sarcastic, even though it contained no disambiguating information. In the present experiments, we found both repetition effects (a benefit for the lexical items) and meaning selection effects (a benefit for the selected meaning of the phrase) with short delays between Stories A and B; with longer delays, only repetition effects were found. Whereas decreasing the elaboration of the phrase eliminated both effects, moving the disambiguating context from before to after the phrase eliminated meaning selection effects only. We conclude that meaning selection effects, which are based on conceptual overlap, are more sensitive to context changes and less robust than repetition effects, which are based on both perceptual and conceptual overlap.

  15. Evaluation of non-reciprocal heterologous immunity between unrelated viruses.

    PubMed

    Che, Jenny W; Selin, Liisa K; Welsh, Raymond M

    2015-08-01

    Heterologous immunity refers to the phenomenon whereby a history of an immune response against one pathogen can provide a level of immunity to a second unrelated pathogen. Previous investigations have shown that heterologous immunity is not necessarily reciprocal, such as in the case of vaccinia virus (VACV). Replication of VACV is reduced in mice immune to a variety of pathogens, while VACV fails to induce immunity to several of the same pathogens, including lymphocytic choriomeningitis virus (LCMV). Here we examine the lack of reciprocity of heterologous immunity between VACV and LCMV and find that they induce qualitatively different memory CD8 T cells. However, depending on the repertoire of an individual host, VACV can provide protection against LCMV simply by experimentally amplifying the quantity of T cells cross-reactive with the two viruses. Thus, one cause for lack of reciprocity is differences in the frequencies of cross-reactive T cells in immune hosts.

  16. BSL-3 laboratory practices in the United States: comparison of select agent and non-select agent facilities.

    PubMed

    Richards, Stephanie L; Pompei, Victoria C; Anderson, Alice

    2014-01-01

    New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non-select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non-select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non-select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non-select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non-select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non-select agent laboratories to improve occupational health and safety. PMID:24552359

  17. Task rescheduling model for resource disruption problem in unrelated parallel processor system

    NASA Astrophysics Data System (ADS)

    Nordin, Syarifah Zyurina; Caccetta, Lou

    2014-07-01

    In this paper, we concentrate on the scheduling problem with interruption occurs in the parallel processor system. The situation happens when the availability of the unrelated parallel processors in the time slot decreases in certain time periods and its define as resource disruption. Our objective is to consider a recovery scheduling option for this issue to overcome the possibilities of having infeasibility of the original scheduling plan. Our approach for the recovery is task rescheduling which is to assign the tasks in the initial schedule plan to reflect the new restrictions. A recovery mixed integer linear programming model is proposed to solve the disruption problem. We also conduct a computational experiment using CPLEX 12.1 solver in AIMMS 3.10 software to analyze the performance of the model.

  18. Rethinking the role of non-selective beta blockers in patients with cirrhosis and portal hypertension.

    PubMed

    Ferrarese, Alberto; Zanetto, Alberto; Germani, Giacomo; Burra, Patrizia; Senzolo, Marco

    2016-08-28

    Non-selective beta blockers (NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics. Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis. PMID:27648153

  19. Multilevel Concatenated Block Modulation Codes for the Frequency Non-selective Rayleigh Fading Channel

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Rhee, Dojun

    1996-01-01

    This paper is concerned with construction of multilevel concatenated block modulation codes using a multi-level concatenation scheme for the frequency non-selective Rayleigh fading channel. In the construction of multilevel concatenated modulation code, block modulation codes are used as the inner codes. Various types of codes (block or convolutional, binary or nonbinary) are being considered as the outer codes. In particular, we focus on the special case for which Reed-Solomon (RS) codes are used as the outer codes. For this special case, a systematic algebraic technique for constructing q-level concatenated block modulation codes is proposed. Codes have been constructed for certain specific values of q and compared with the single-level concatenated block modulation codes using the same inner codes. A multilevel closest coset decoding scheme for these codes is proposed.

  20. Rethinking the role of non-selective beta blockers in patients with cirrhosis and portal hypertension

    PubMed Central

    Ferrarese, Alberto; Zanetto, Alberto; Germani, Giacomo; Burra, Patrizia; Senzolo, Marco

    2016-01-01

    Non-selective beta blockers (NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics. Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis. PMID:27648153

  1. Predators reduce abundance and species richness of coral reef fish recruits via non-selective predation

    NASA Astrophysics Data System (ADS)

    Heinlein, J. M.; Stier, A. C.; Steele, M. A.

    2010-06-01

    Predators have important effects on coral reef fish populations, but their effects on community structure have only recently been investigated and are not yet well understood. Here, the effect of predation on the diversity and abundance of young coral reef fishes was experimentally examined in Moorea, French Polynesia. Effects of predators were quantified by monitoring recruitment of fishes onto standardized patch reefs in predator-exclosure cages or uncaged reefs. At the end of the 54-day experiment, recruits were 74% less abundant on reefs exposed to predators than on caged ones, and species richness was 42% lower on reefs exposed to predators. Effects of predators varied somewhat among families, however, rarefaction analysis indicated that predators foraged non-selectively among species. These results indicate that predation can alter diversity of reef fish communities by indiscriminately reducing the abundance of fishes soon after settlement, thereby reducing the number of species present on reefs.

  2. Rethinking the role of non-selective beta blockers in patients with cirrhosis and portal hypertension

    PubMed Central

    Ferrarese, Alberto; Zanetto, Alberto; Germani, Giacomo; Burra, Patrizia; Senzolo, Marco

    2016-01-01

    Non-selective beta blockers (NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics. Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis.

  3. Computer applications in the search for unrelated stem cell donors.

    PubMed

    Müller, Carlheinz R

    2002-08-01

    The majority of patients which are eligible for a blood stem cell transplantation from an allogeneic donor do not have a suitable related donor so that an efficient unrelated donor search is a prerequisite for this treatment. Currently, there are over 7 million volunteer donors in the files of 50 registries in the world and in most countries the majority of transplants are performed from a foreign donor. Evidently, computer and communication technology must play a crucial role in the complex donor search process on the national and international level. This article describes the structural elements of the donor search process and discusses major systematic and technical issues to be addressed in the development and evolution of the supporting telematic systems. The theoretical considerations are complemented by a concise overview over the current state of the art which is given by describing the scope, relevance, interconnection and technical background of three major national and international computer appliances: The German Marrow Donor Information System (GERMIS) and the European Marrow Donor Information System (EMDIS) are interoperable business-to-business e-commerce systems and Bone Marrow Donors World Wide (BMDW) is the basic international donor information desk on the web. PMID:12216954

  4. Computer applications in the search for unrelated stem cell donors.

    PubMed

    Müller, Carlheinz R

    2002-08-01

    The majority of patients which are eligible for a blood stem cell transplantation from an allogeneic donor do not have a suitable related donor so that an efficient unrelated donor search is a prerequisite for this treatment. Currently, there are over 7 million volunteer donors in the files of 50 registries in the world and in most countries the majority of transplants are performed from a foreign donor. Evidently, computer and communication technology must play a crucial role in the complex donor search process on the national and international level. This article describes the structural elements of the donor search process and discusses major systematic and technical issues to be addressed in the development and evolution of the supporting telematic systems. The theoretical considerations are complemented by a concise overview over the current state of the art which is given by describing the scope, relevance, interconnection and technical background of three major national and international computer appliances: The German Marrow Donor Information System (GERMIS) and the European Marrow Donor Information System (EMDIS) are interoperable business-to-business e-commerce systems and Bone Marrow Donors World Wide (BMDW) is the basic international donor information desk on the web.

  5. [Problems of cardiovascular toxicity of coxibs and non-selective NSA].

    PubMed

    Forejtová, S

    2006-01-01

    Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs. Certain observation studies indicate that they are used by 20 to 30% of population of developed countries. The most common NSA's adverse effects are gastrointestinal complications. Coxibs have been developed as an alternative to conventional non-selective NSA; with similar efficacy, they should reduce the risk of development of gastrointestinal complications. In the few last years, possible toxicity of coxibs and other non-steroidal antirheumatics has been widely discussed. The VIGOR study, which was performed 6 years ago, showed five times higher incidence of nonfatal myocardial infarction in patients with rofecoxib therapy as compared with naproxen. Afterwards, there was much debate about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and confuted at the same time. Possible cardioprotective effect of naproxen was discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily. In the end of 2004, three controversial studies on celecoxib were published. Although the first study (Adenoma Prevention with Celecoxib study, APC) showed higher cardiovascular risk of celecoxib, the second study (Prevention of Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase of the risk of cardiovascular (CV) toxicity of naproxen. In the last year, researchers have tried to decide whether CV toxicity is a class effect of coxib group or a class effect of all NSA. Many observation studies proved higher CV risk both of coxibs (particularly rofecoxib) and non-selective NSA including naproxen. These new findings moved the American FDA (Food and Drug Administration) to publish guidance concerning higher CV risk of all coxibs and NSA. For the time being, the EMEA (European Agency for Evaluation

  6. DYRK1A mutations in two unrelated patients.

    PubMed

    Ruaud, Lyse; Mignot, Cyril; Guët, Agnès; Ohl, Christelle; Nava, Caroline; Héron, Delphine; Keren, Boris; Depienne, Christel; Benoit, Valérie; Maystadt, Isabelle; Lederer, Damien; Amsallem, Daniel; Piard, Juliette

    2015-03-01

    The Dual-specify tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene has been extensively studied for its role in the pathophysiology of intellectual disability (ID) in Down syndrome. The rise of next generation sequencing (NGS) and array-CGH (aCGH) in diagnostic settings for the evaluation of patients with ID allowed the identification of 17 patients carrying heterozygous genetic aberrations involving DYRK1A to date. The rate of DYRK1A mutations in this population reaches >1% in published NGS studies. The current report aims at further defining the phenotype of this encephalopathy with the detailed report of two unrelated patients. Both patients were boys with developmental delay, febrile seizures, facial dysmorphism and brain atrophy on MRI. Patient #1 had autistic behaviors and micropenis and Patient #2 had stereotypies and microcephaly. NGS analyses identified heterozygous de novo variants in DYRK1A: the c.613C >T (p.Arg205*) nonsense mutation in Patient #1 and the c.932C >T (p.Ser311Phe) missense mutation in Patient #2. Together with previously reported cases, patients with DYRK1A mutations share many clinical features and may have a recognizable phenotype that includes, by decreasing order of frequency: developmental delay or ID with behaviors suggesting autism spectrum disorder, microcephaly, epileptic seizures, facial dysmorphism including ear anomalies (large ears, hypoplastic lobes), thin lips, short philtrum and frontal bossing. Delineation of the phenotype/genotype correlation is not feasible at the moment and will be a challenge for the coming years. PMID:25641759

  7. Fast model-based estimation of ancestry in unrelated individuals.

    PubMed

    Alexander, David H; Novembre, John; Lange, Kenneth

    2009-09-01

    Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure. Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure. We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure. However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies.

  8. Endogenous pain inhibition is unrelated to autonomic responses in acute whiplash-associated disorders.

    PubMed

    De Kooning, Margot; Daenen, Liesbeth; Roussel, Nathalie; Cras, Patrick; Buyl, Ronald; Ickmans, Kelly; Struyf, Filip; Nijs, Jo

    2015-01-01

    Patients with acute whiplash-associated disorder (WAD) demonstrate an inefficient endogenous pain inhibition and may experience a dysfunction in autonomic nervous system reactivity to pain. This study compared the autonomic response to painful stimuli between patients with acute and chronic WAD and healthy controls. In addition, the role of the autonomic nervous system for explaining inefficient endogenous pain inhibition was examined in acute WAD. Seventeen patients with acute WAD, 30 patients with chronic WAD, and 31 healthy controls participated in an experiment evaluating the autonomic nervous system at rest and during painful stimuli. Skin conductance and heart rate variability (HRV) parameters were monitored continuously during conditioned pain modulation. A significant autonomic response to pain was present for skin conductance and two HRV parameters in all experimental groups. There was an interaction effect in the skin conductance response to pain but not in HRV responses in any of the groups. In patients with acute WAD, no significant correlations were present between pain, pressure pain thresholds, pain inhibition, and any of the autonomic parameters. This study refutes autonomic dysfunction at rest and in response to pain in acute WAD. The dysfunctional conditioned pain modulation appears unrelated to autonomic responses to pain. PMID:26348457

  9. Endogenous pain inhibition is unrelated to autonomic responses in acute whiplash-associated disorders.

    PubMed

    De Kooning, Margot; Daenen, Liesbeth; Roussel, Nathalie; Cras, Patrick; Buyl, Ronald; Ickmans, Kelly; Struyf, Filip; Nijs, Jo

    2015-01-01

    Patients with acute whiplash-associated disorder (WAD) demonstrate an inefficient endogenous pain inhibition and may experience a dysfunction in autonomic nervous system reactivity to pain. This study compared the autonomic response to painful stimuli between patients with acute and chronic WAD and healthy controls. In addition, the role of the autonomic nervous system for explaining inefficient endogenous pain inhibition was examined in acute WAD. Seventeen patients with acute WAD, 30 patients with chronic WAD, and 31 healthy controls participated in an experiment evaluating the autonomic nervous system at rest and during painful stimuli. Skin conductance and heart rate variability (HRV) parameters were monitored continuously during conditioned pain modulation. A significant autonomic response to pain was present for skin conductance and two HRV parameters in all experimental groups. There was an interaction effect in the skin conductance response to pain but not in HRV responses in any of the groups. In patients with acute WAD, no significant correlations were present between pain, pressure pain thresholds, pain inhibition, and any of the autonomic parameters. This study refutes autonomic dysfunction at rest and in response to pain in acute WAD. The dysfunctional conditioned pain modulation appears unrelated to autonomic responses to pain.

  10. α-Synuclein forms non-selective cation channels and stimulates ATP-sensitive potassium channels in hippocampal neurons

    PubMed Central

    Mironov, Sergej L

    2015-01-01

    In Parkinson's disease and several other neurodegenerative diseases, the protein α-synuclein (αS) is produced within neurons and accumulates in the extracellular fluid. Several mechanisms of αS action are proposed, one of which is the formation of cation-permeable pores that may mediate toxicity. αS induces non-selective cation channels in lipid bilayers, but whether this occurs in living neurons and which properties the channels possess have not yet been examined. In this study the properties of αS channels in dissociated hippocampal neurons are documented. In cell-attached recordings the incorporation of αS into membranes was driven by applied negative potentials. These channels exhibited multiple levels of conductance (30, 70 and 120 pS at −100 mV) and inward rectification. The persistent activity of αS channels induced local changes in intracellular Na+ and Ca2+, depolarized neurons and augmented bursting activity. αS channels formed by adding αS to the intracellular membrane in inside-out patches exhibited outward rectification. αS channels were equally permeable to Na+, K+ and Ca2+. These channels were also observed in neurons transfected with wild-type or mutant A53T αS, and after extracellular application of wild-type or mutant A53T αS proteins. Opening of αS channels stimulated opening of ATP-sensitive K+ (KATP ) channels and did not interfere with the activity of delayed rectifier K+ channels. The properties of αS channels in neuronal membranes suggest stronger toxicity of extracellularly applied αS than intracellular αS. Enhancement of neuronal excitability and distortions in ion homeostasis may underlie the toxic effects of αS that can be dampened by KATP channels. PMID:25556793

  11. Horizontal cells of the rabbit retina are non-selectively connected to the cones.

    PubMed

    Hack, I; Peichl, L

    1999-07-01

    Mammalian horizontal cells have generally been assumed to be spectrally non-selective in their cone contacts until recently, when specific contacts have been found for some species. The rabbit retina is frequently studied as a representative of dichromatic mammalian retinae. These are the reasons for elucidating the connections of the two types of horizontal cells (A-HCs and B-HCs) with the green-sensitive and blue-sensitive cones of the rabbit retina. Individual A-HCs and B-HCs were revealed by Lucifer Yellow injections, the total cone population overlying them was stained using peanut agglutinin, and the blue cones among these were identified by the antiserum JH 455 against blue cone opsin. Both A-HCs and B-HCs indiscriminately contact the two cone types available. This holds for the green cone-dominated dorsal retina and the blue cone-dominated ventral retina. No evidence was found for a third, potentially blue cone-selective, horizontal cell type [postulated by Famiglietti, E. V. (1990) Brain Res., 535, 174-179].

  12. Differences of binding characteristics of non-selective opiates towards and delta receptor types

    SciTech Connect

    Delay-Goyet, P.; Roques, B.P.; Zajac, J.M.

    1987-08-10

    (TH)ET (etorphine), which is considered either as an universal ligand or a agonist, interacts with identical affinities K/sub D/ = 0.33 - 0.38 nM to hybrid cells and rabbit cerebellum, pure delta and -enriched opioid receptor preparations, respectively. In rat brain tissue, (TH)ET binding is inhibited by DAGO (Tyr-D-Ala-Gly-(Me)-Phe-Gly-ol), a selective agonist, in a competitive manner without apparent modification of the maximal number of sites. Furthermore, even at a DAGO concentration (300 nM) which should be sufficient to block (TH)ET interaction with sites, no variation in the total capacity of the tritiated ligand is observed. In contrast, DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr), a delta-preferential agonist, blocks (TH)ET binding in rat brain at a concentration able to saturate delta-sites. At higher concentrations, where DTLET cross reacts with -sites, this ligand exhibits similar properties to those of DAGO. These data are very different from those obtained with (TH)EKC (ethylketocyclazocine), another universal ligand, the binding properties of which are easily explained by the occurrence in rat brain tissue of independent sites exhibiting pharmacological profiles of , delta and kappa sites. The authors results underline the possible misinterpretation of binding data obtained by using (TH) etorphine as a non-selective ligand. 28 references, 1 figure, 2 tables.

  13. 26 CFR 1.105-3 - Payments unrelated to absence from work.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Payments unrelated to absence from work. 1.105-3... Payments unrelated to absence from work. Section 105(c) provides an exclusion from gross income with... absent from work. Loss of use or disfigurement shall be considered permanent when it may reasonably...

  14. 26 CFR 1.105-3 - Payments unrelated to absence from work.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Payments unrelated to absence from work. 1.105-3... Payments unrelated to absence from work. Section 105(c) provides an exclusion from gross income with... absent from work. Loss of use or disfigurement shall be considered permanent when it may reasonably...

  15. 26 CFR 1.105-3 - Payments unrelated to absence from work.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Payments unrelated to absence from work. 1.105-3... Payments unrelated to absence from work. Section 105(c) provides an exclusion from gross income with... absent from work. Loss of use or disfigurement shall be considered permanent when it may reasonably...

  16. Interaction profile of macitentan, a new non-selective endothelin-1 receptor antagonist, in vitro.

    PubMed

    Weiss, Johanna; Theile, Dirk; Rüppell, Maximilian Alexander; Speck, Tobias; Spalwisz, Adriana; Haefeli, Walter Emil

    2013-02-15

    Macitentan is a new non-selective endothelin-1 receptor antagonist under development for the treatment of pulmonary arterial hypertension. Information on the potential for macitentan to influence the pharmacokinetics of concomitantly administered drugs by inhibition or induction of drug metabolising enzymes or drug transporters is sparse. We therefore studied the potential of macitentan to inhibit and induce critical targets of drug metabolism and drug distribution (transporters) in vitro. Induction was quantified at the mRNA level by real-time RT-PCR in LS180 cells and revealed that macitentan significantly induced mRNA expression of cytochrome P450 3A4 (CYP3A4), P-glycoprotein (P-gp, ABCB1), solute carrier of organic anions 1B1 (SLCO1B1), and uridinediphosphate-glucuronosyltransferase 1A3 (UGT1A9). By means of a reporter gene assay our study establishes macitentan as a potent activator of pregnane X receptor (PXR). Inhibition of drug transporters was evaluated by using transporter over-expressing cell lines and fluorescent specific substrates of the respective transporters and revealed that macitentan is an inhibitor of P-gp, breast cancer resistance protein (BCRP), SLCO1B1, and SLCO1B3. Using commercial kits macitentan was demonstrated to be a moderate inhibitor of CYP3A4 and CYP2C19. In conclusion our data provide a comprehensive analysis of the interaction profile of macitentan with drug metabolising and transporting enzymes in vitro. Although macitentan has a similar or higher potency for induction and inhibition of drug metabolising enzymes and transporters than bosentan, its low plasma concentrations and minimal accumulation in the liver suggest that it will be markedly less prone to drug-drug interactions than bosentan.

  17. Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments.

    PubMed

    Wichgers Schreur, Paul J; Kortekaas, Jeroen

    2016-08-01

    The bunyavirus genome comprises a small (S), medium (M), and large (L) RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH), the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV) genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process. PMID:27548280

  18. Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments

    PubMed Central

    Wichgers Schreur, Paul J.; Kortekaas, Jeroen

    2016-01-01

    The bunyavirus genome comprises a small (S), medium (M), and large (L) RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH), the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV) genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process. PMID:27548280

  19. Adoptable strategic approaches to improve outcomes of allogeneic peripheral blood stem cell transplantations from unrelated donors.

    PubMed

    Sohn, Sang Kyun; Moon, Joon Ho

    2014-06-01

    While previous studies have shown comparable clinical results for related and unrelated bone marrow transplantation (BMT), the transplantation outcomes for related and unrelated peripheral blood stem cell transplantation (PBSCT) may not follow the same pattern due to a higher incidence of graft-versus-host disease (GVHD)-related morbidity and mortality in the case of long-term survival after unrelated PBSCT. Thus, given the higher possibility of an impaired quality of life due to severe GVHD in long-term survivors who receive unrelated PBSCT, the selection of the stem cell source needs to be decided very carefully. In addition, strategic approaches, such as the extended use of immunosuppressant as a GVHD prophylaxis, the use of antithymocyte globulins (ATGs), choosing a younger donor, and optimizing the CD34+ cell dose, need to be adopted to improve the transplantation outcomes by minimizing GVHD-related morbidity and mortality in an unrelated PBSCT setting. This review article provides a comparison of BMT and PBSCT, and related and unrelated PBSCT, plus introduces several adoptable strategies to improve the outcomes of unrelated PBSCT.

  20. Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

    PubMed Central

    Anasetti, Claudio; Logan, Brent R.; Lee, Stephanie J.; Waller, Edmund K.; Weisdorf, Daniel J.; Wingard, John R.; Cutler, Corey S.; Westervelt, Peter; Woolfrey, Ann; Couban, Stephen; Ehninger, Gerhard; Johnston, Laura; Maziarz, Richard T.; Pulsipher, Michael A.; Porter, David L.; Mineishi, Shin; McCarty, John M.; Khan, Shakila P.; Anderlini, Paolo; Bensinger, William I.; Leitman, Susan F.; Rowley, Scott D.; Bredeson, Christopher; Carter, Shelly L.; Horowitz, Mary M.; Confer, Dennis L.

    2012-01-01

    BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P = 0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P = 0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P = 0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral

  1. Living unrelated kidney donors: ethical aspects of living kidney donation in Brazil.

    PubMed

    Ferreira, Gustavo Fernandes; Guedes, Clarissa Diniz

    2011-01-01

    Brazil has established the largest public kidney transplantation system in the world .46.2% of transplants in 2008 came from living donors. The vast majority of these involved relatives of the recipient; less than 8% came from unrelated donors. In 2008, Brazil's health minister proposed banning unrelated donors in kidney transplantation. A large number of the over 35,000 Brazilians on the waiting list for a kidney would be denied a transplant without the use of unrelated donors. Brazilian culture has a unique feature, the "informal family", that is not legally recognised as a "family entity and is bound by affection rather than genetic or legal ties. It is vital that Brazil establishes a regulated, standardised, and ethical system of organ procurement; creates awareness about transplantation in physicians and the public; upgrades facilities and standardises medical care, and enforces legislation for transplantation. However, outlawing the use of unrelated donors would result in injustice for many patients who seek kidneys.

  2. Modulation by purines of calcium-activated non-selective cation channels in the outer hair cells of the guinea-pig cochlea.

    PubMed Central

    Van den Abbeele, T; Tran Ba Huy, P; Teulon, J

    1996-01-01

    1. The cell-attached and cell-free configurations of the patch-clamp technique were used to investigate whether external ATP and its derivatives modulate channel activity in outer hair cells freshly isolated from the guinea-pig cochlea. 2. Submicromolar concentrations of ATP stimulated a non-selective cation channel with a conductance of about 25 pS. The ATP-elicited stimulation was partly blocked by the membrane-permeant blocker 3',5-dichlorodiphenylamine-2-carboxylic acid (DCDPC), and mimicked by the calcium ionophore, ionomycin, suggesting that the channel activated by ATP is identical to a previously reported calcium-activated non-selective (CAN) cation channel. 3. The P2x agonist beta, gamma-methylene-ATP (beta, gamma-MeATP, 10 microM) and the P2Y agonist 2-methyl-thio-ATP (2-MeSATP, 1 microM) both activated CAN channels. The effect of ATP was inhibited by the P2 antagonist suramin but not by the P2Y antagonist Reactive Blue 2. These results suggest that both purinergic receptors are involved in the ATP-evoked response and that internal calcium acts as a second messenger for opening CAN channels. 4. In contrast, adenosine inhibited CAN channels. This effect was reproduced by the A2 agonist 5'-N-ethylcarboxyamidoadenosine (NECA) and the permeant cAMP analogue 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), but not by the A1 agonist N6-cyclo-hexyladenosine (CHA). CAN channels were also inhibited when the catalytic subunit of protein kinase A was applied internally on inside-out patches, suggesting that adenosine A2 receptor downregulates CAN channels via a cAMP-dependent phosphorylation. Images Figure 10 PMID:8814608

  3. 48 CFR 1852.228-78 - Cross-waiver of liability for science or space exploration activities unrelated to the...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... for science or space exploration activities unrelated to the International Space Station. 1852.228-78... Cross-waiver of liability for science or space exploration activities unrelated to the International... Liability for Science or Space Exploration Activities Unrelated to the International Space Station (OCT...

  4. 48 CFR 1852.228-78 - Cross-waiver of liability for science or space exploration activities unrelated to the...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... for science or space exploration activities unrelated to the International Space Station. 1852.228-78... Cross-waiver of liability for science or space exploration activities unrelated to the International... Liability for Science or Space Exploration Activities Unrelated to the International Space Station (OCT...

  5. Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.

    PubMed

    Chen, Xuqin; Gill, Deepak; Shaw, Peter; Ouvrier, Robert; Troedson, Christopher

    2016-03-01

    The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed. All three transplanted patients remain well, and the parameters evaluated remain stable. Of the treated patients, the two sisters had ongoing evidence of demyelinating sensorimotor neuropathy on nerve conduction tests, and with a early sensorimotor neuropathy in the older sister , and the other patient has mild intellectual impairment. One of the two un-transplanted controls, 15 years after MLD diagnosis, has relentlessly progressed to full dependency with epilepsy, severe mental retardation, dystonic movements, dysphagia and recurrent respiratory problems. Six years after diagnosis, the other control has a slowly progressive course with spastic dystonic quadriplegia, epilepsy, dysphagia, continual drooling and incontinence. Our data show that, in comparison with their untreated siblings, UCBT significantly slowed the progression of the disease in the treated patients. We conclude that UCBT benefits children with pre-symptomatic early juvenile onset MLD by favourably altering the natural history of the disease.

  6. Characterization of two unrelated satellite DNA families in the Colorado potato beetle Leptinotarsa decemlineata (Coleoptera, Chrysomelidae).

    PubMed

    Lorite, Pedro; Torres, M Isabel; Palomeque, Teresa

    2013-10-01

    The Colorado potato beetle (Leptinotarsa decemlineata, family Chrysomelidae),a phytophagous insect, which feeds preferably on potatoes, constitutes a serious pest of this crop and causes extensive damage to tomatoes and egg plants. It has a remarkable ability to develop resistance quickly against insecticides and shows a diversified and flexible life history. Consequently, the control of this pest has become difficult, requiring the development of new alternative biotechnology-based strategies. Such strategies require a thorough knowledge of the beetle’s genome,including the repetitive DNA. Satellite DNA (stDNA), composed of long arrays of tandemly arranged repeat units, constitutes the major component of heterochromatin and is located mainly in centromeric and telomeric chromosomal regions. We have studied two different unrelated satellite-DNA families of which the consensus sequences were 295 and 109bp in length, named LEDE-I and LEDE-II, respectively.Both were AT-rich (70.8% and 71.6%, respectively). Predictive models of sequence-dependent DNA bending and the study of electrophoretic mobility on non-denaturing polyacrylamide gels have shown that the DNA was curved in both satellite-DNA families. Among other features, the chromosome localization of both stDNAs has been studied. In situ hybridization performed on meiotic and mitoticnuclei showed chromosomes, including the X chromosome, with zero, one, or two stDNAs. In recent years, it has been proposed that the repetitive DNA may play a key role in biological diversification processes. This is the first molecular and cytogenetic study conducted on L. decemlineata repetitive DNA and specifically on stDNA, which is one of the important constituents of eukaryotic genomes.

  7. Characterization of two unrelated satellite DNA families in the Colorado potato beetle Leptinotarsa decemlineata (Coleoptera, Chrysomelidae).

    PubMed

    Lorite, Pedro; Torres, M Isabel; Palomeque, Teresa

    2013-10-01

    The Colorado potato beetle (Leptinotarsa decemlineata, family Chrysomelidae),a phytophagous insect, which feeds preferably on potatoes, constitutes a serious pest of this crop and causes extensive damage to tomatoes and egg plants. It has a remarkable ability to develop resistance quickly against insecticides and shows a diversified and flexible life history. Consequently, the control of this pest has become difficult, requiring the development of new alternative biotechnology-based strategies. Such strategies require a thorough knowledge of the beetle’s genome,including the repetitive DNA. Satellite DNA (stDNA), composed of long arrays of tandemly arranged repeat units, constitutes the major component of heterochromatin and is located mainly in centromeric and telomeric chromosomal regions. We have studied two different unrelated satellite-DNA families of which the consensus sequences were 295 and 109bp in length, named LEDE-I and LEDE-II, respectively.Both were AT-rich (70.8% and 71.6%, respectively). Predictive models of sequence-dependent DNA bending and the study of electrophoretic mobility on non-denaturing polyacrylamide gels have shown that the DNA was curved in both satellite-DNA families. Among other features, the chromosome localization of both stDNAs has been studied. In situ hybridization performed on meiotic and mitoticnuclei showed chromosomes, including the X chromosome, with zero, one, or two stDNAs. In recent years, it has been proposed that the repetitive DNA may play a key role in biological diversification processes. This is the first molecular and cytogenetic study conducted on L. decemlineata repetitive DNA and specifically on stDNA, which is one of the important constituents of eukaryotic genomes. PMID:23448367

  8. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia

    PubMed Central

    Zhang, Mei-Jie; Bacigalupo, Andrea A.; Bashey, Asad; Appelbaum, Frederick R.; Aljitawi, Omar S.; Armand, Philippe; Antin, Joseph H.; Chen, Junfang; Devine, Steven M.; Fowler, Daniel H.; Luznik, Leo; Nakamura, Ryotaro; O’Donnell, Paul V.; Perales, Miguel-Angel; Pingali, Sai Ravi; Porter, David L.; Riches, Marcie R.; Ringdén, Olle T. H.; Rocha, Vanderson; Vij, Ravi; Weisdorf, Daniel J.; Champlin, Richard E.; Horowitz, Mary M.; Fuchs, Ephraim J.; Eapen, Mary

    2015-01-01

    We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P = .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P = .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P = .05) and 34% vs 52% (P = .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P = .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P = .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. PMID:26130705

  9. 26 CFR 1.514(a)-1 - Unrelated debt-financed income and deductions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... preceding sentence shall be determined in accordance with the rules set forth in subchapter P, chapter 1 of... for its stock, see § 1.514(d)-1. (iv) Example. This subparagraph may be illustrated by the following... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Unrelated debt-financed income and deductions....

  10. Motivation, Intentionality, and Mind Wandering: Implications for Assessments of Task-Unrelated Thought

    ERIC Educational Resources Information Center

    Seli, Paul; Cheyne, James Allan; Xu, Mengran; Purdon, Christine; Smilek, Daniel

    2015-01-01

    Researchers of mind wandering frequently assume that (a) participants are motivated to do well on the tasks they are given, and (b) task-unrelated thoughts (TUTs) that occur during task performance reflect unintentional, unwanted thoughts that occur despite participants' best intentions to maintain task-focus. Given the relatively boring and…

  11. 26 CFR 1.511-3 - Provisions generally applicable to the tax on unrelated business income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... unrelated business income. 1.511-3 Section 1.511-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income... business income. (a) Assessment and collections. Since the taxes imposed by section 511 are taxes...

  12. The Law of Private Inurement and Unrelated Income Taxation: Implications for Colleges and Universities

    ERIC Educational Resources Information Center

    Myers, John Holt

    1975-01-01

    Trends in the federal tax law doctrines of unrelated trade or business and private inurement are surveyed with the conclusion that certain proscribed transactions with insiders would cause deprivation of tax-exempt status while other activities, bearing more on private than public interests, may cause some tax liability rather than total loss of…

  13. 20 CFR 404.1522 - When you have two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false When you have two or more unrelated impairments-initial claims. 404.1522 Section 404.1522 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and...

  14. 20 CFR 404.1522 - When you have two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false When you have two or more unrelated impairments-initial claims. 404.1522 Section 404.1522 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and...

  15. 20 CFR 404.1522 - When you have two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false When you have two or more unrelated impairments-initial claims. 404.1522 Section 404.1522 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and...

  16. 20 CFR 404.1522 - When you have two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false When you have two or more unrelated impairments-initial claims. 404.1522 Section 404.1522 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and...

  17. 20 CFR 404.1522 - When you have two or more unrelated impairments-initial claims.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false When you have two or more unrelated impairments-initial claims. 404.1522 Section 404.1522 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and...

  18. Event-Related EEG Oscillations to Semantically Unrelated Words in Normal and Learning Disabled Children

    ERIC Educational Resources Information Center

    Fernandez, Thalia; Harmony, Thalia; Mendoza, Omar; Lopez-Alanis, Paula; Marroquin, Jose Luis; Otero, Gloria; Ricardo-Garcell, Josefina

    2012-01-01

    Learning disabilities (LD) are one of the most frequent problems for elementary school-aged children. In this paper, event-related EEG oscillations to semantically related and unrelated pairs of words were studied in a group of 18 children with LD not otherwise specified (LD-NOS) and in 16 children with normal academic achievement. We propose that…

  19. 26 CFR 1.141-9 - Unrelated or disproportionate use test.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... uses $18.1 million of the proceeds for construction of a new school building and $1.9 million of the proceeds for construction of a privately operated cafeteria in its administrative office building, which is... is unrelated to the government use (that is, school construction) financed with the bonds and...

  20. 26 CFR 1.141-9 - Unrelated or disproportionate use test.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... uses $18.1 million of the proceeds for construction of a new school building and $1.9 million of the proceeds for construction of a privately operated cafeteria in its administrative office building, which is... is unrelated to the government use (that is, school construction) financed with the bonds and...

  1. 26 CFR 1.141-9 - Unrelated or disproportionate use test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... uses $18.1 million of the proceeds for construction of a new school building and $1.9 million of the proceeds for construction of a privately operated cafeteria in its administrative office building, which is... is unrelated to the government use (that is, school construction) financed with the bonds and...

  2. 26 CFR 1.141-9 - Unrelated or disproportionate use test.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... uses $18.1 million of the proceeds for construction of a new school building and $1.9 million of the proceeds for construction of a privately operated cafeteria in its administrative office building, which is... is unrelated to the government use (that is, school construction) financed with the bonds and...

  3. 26 CFR 1.141-9 - Unrelated or disproportionate use test.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... uses $18.1 million of the proceeds for construction of a new school building and $1.9 million of the proceeds for construction of a privately operated cafeteria in its administrative office building, which is... is unrelated to the government use (that is, school construction) financed with the bonds and...

  4. Frequent occurrence of highly expanded but unrelated B-cell clones in patients with multiple myeloma.

    PubMed

    Kriangkum, Jitra; Motz, Sarah N; Debes Marun, Carina S; Lafarge, Sandrine T; Gibson, Spencer B; Venner, Christopher P; Johnston, James B; Belch, Andrew R; Pilarski, Linda M

    2013-01-01

    Clonal diversity in multiple myeloma (MM) includes both MM-related and MM-unrelated clonal expansions which are subject to dominance exerted by the MM clone. Here we show evidence for the existence of minor but highly expanded unrelated B-cell clones in patients with MM defined by their complementary determining region 3 (CDR3) peak. We further characterize these clones over the disease and subsequent treatment. Second clones were identified by their specific IgH-VDJ sequences that are distinct from those of dominant MM clones. Clonal frequencies were determined through semi-quantitative PCR, quantitative PCR and single-cell polymerase chain reaction of the clone-specific sequence. In 13/74 MM patients, more than one dominant CDR3 peak was identified with 12 patients (16%) being truly biclonal. Second clones had different frequencies, were found in different locations and were found in different cell types from the dominant MM clone. Where analysis was possible, they were shown to have chromosomal characteristic distinct from those of the MM clone. The frequency of the second clone also changed over the course of the disease and often persisted despite treatment. Molecularly-defined second clones are infrequent in monoclonal gammopathy of undetermined significance (MGUS, 1/43 individuals or 2%), suggesting that they may arise at relatively late stages of myelomagenesis. In further support of our findings, biclonal gammopathy and concomitant MM and CLL (chronic lymphocytic leukemia) were confirmed to originate from two unrelated clones. Our data supports the idea that the clone giving rise to symptomatic myeloma exerts clonal dominance to prevent expansion of other clones. MM and second clones may arise from an underlying niche permissive of clonal expansion. The clinical significance of these highly expanded but unrelated clones remains to be confirmed. Overall, our findings add new dimensions to evaluating related and unrelated clonal expansions in MM and the

  5. Incipient allochronic speciation due to non-selective assortative mating by flowering time, mutation and genetic drift

    PubMed Central

    Devaux, Céline; Lande, Russell

    2008-01-01

    We model the evolution of flowering time using a multilocus quantitative genetic model with non-selective assortative mating and mutation to investigate incipient allochronic speciation in a finite population. For quantitative characters with evolutionary parameters satisfying empirical observations and two approximate inequalities that we derived, disjunct clusters in the population flowering phenology originated within a few thousand generations in the absence of disruptive natural or sexual selection. Our simulations and the conditions we derived showed that cluster formation was promoted by limited population size, high mutational variance of flowering time, short individual flowering phenology and a long flowering season. By contrast, cluster formation was hindered by inbreeding depression, stabilizing selection and pollinator limitation. Our results suggest that incipient allochronic speciation in populations of limited size (satisfying two inequalities) could be a common phenomenon. PMID:18700202

  6. Home point-of-care international normalised ratio monitoring sustained by a non-selective educational program in children.

    PubMed

    Bajolle, Fanny; Lasne, Dominique; Elie, Caroline; Cheurfi, Radhia; Grazioli, Aurélie; Traore, Maladon; Souillard, Patrick; Boudjemline, Younes; Jourdain, Patrick; Bonnet, Damien

    2012-10-01

    Adverse events related to vitamin K antagonist (VKA) therapy might be reduced by point-of-care international normalised ratio (POC INR) monitoring supported by an education program (EP). Our aim was to evaluate the efficacy of a non-selective VKA paediatric EP (regardless of the social, economic, educational or linguistic levels) by analysing the time spent in the therapeutic range (TTR), VKA adverse events and compliance to treatment, and INR control prescriptions. The EP was modified from the pediatric EP previously described but improved by a specifically devised child-focused game. One hundred four consecutive children (median age 8 years) receiving VKA were included in a standardised EP. Patients were in self-testing, and dose adjustments were made by a single physician for three tolerance ranges according to the underlying disease: [2.5-4], [1.8-3.2], and [1.5-2.5]. The median follow-up was 481 days [70-1,001]. The overall TTR was 81.4% [36-100]. The TTR were 74%, 85.6% and 89% for the ranges [2.5-4], [1.8-3.2], and [1.5-2.5], respectively. These results were sustainable during the study period. Only one serious VKA adverse event was recorded. The median number of POC INR tests was 2.5 [1.6-5.7] INR per patient and month. Patients/families performed POC INR when requested in 86.9% of the cases. More than 90% of the families found the EP supportive and wished to follow a long-term reinforcement program. In conclusion, this non-selective child-focused EP for VKA therapy, strongly supported by our dedicated game, is useful in maintaining efficacy, safety and compliance to anticoagulation and its monitoring.

  7. Social bonds between unrelated females increase reproductive success in feral horses.

    PubMed

    Cameron, Elissa Z; Setsaas, Trine H; Linklater, Wayne L

    2009-08-18

    In many mammals, females form close social bonds with members of their group, usually between kin. Studies of social bonds and their fitness benefits have not been investigated outside primates, and are confounded by the relatedness between individuals in primate groups. Bonds may arise from kin selection and inclusive fitness rather than through direct benefits of association. However, female equids live in long-term social groups with unrelated members. We present 4 years of behavioral data, which demonstrate that social integration between unrelated females increases both foal birth rates and survival, independent of maternal habitat quality, social group type, dominance status, and age. Also, we show that such social integration reduces harassment by males. Consequently, social integration has strong direct fitness consequences between nonrelatives, suggesting that social bonds can evolve based on these direct benefits alone. Our results support recent studies highlighting the importance of direct benefits in maintaining cooperative behavior, while controlling for the confounding influence of kinship.

  8. Genetic evolution of bacteriophage. I. Hybrids between unrelated bacteriophages P22 and Fels 2.

    PubMed

    Yamamoto, N

    1969-01-01

    A new bacteriophage species, designated F22, was isolated from phage P22 stocks grown on Salmonella typhimurium Q1 lysogenic for Fels 2 at a frequency of less than 10(-11). P22 has a very short tail with a hexagonal base plate and six spikes. Phage Fels 2 is morphologically similar to E. coli T-even phages, having a long tail with a contractile sheath and carrying no genetic region related to P22. Phage F22 is morphologically and serologically indistinguishable from Fels 2, but carries the c(c(1), c(2), and c(3)) markers of P22. The color markers h(21), g, and m(3) of P22 do not appear in F22. Thus, F22 is evidently a recombinant between the unrelated bacteriophages P22 and Fels 2. The recombination between unrelated bacteriophages could play an important role in the evolution of bacteriophages.

  9. Comparable results in patients with acute lymphoblastic leukemia after related and unrelated stem cell transplantation.

    PubMed

    Dahlke, J; Kröger, N; Zabelina, T; Ayuk, F; Fehse, N; Wolschke, C; Waschke, O; Schieder, H; Renges, H; Krüger, W; Kruell, A; Hinke, A; Erttmann, R; Kabisch, H; Zander, A R

    2006-01-01

    We report the results of 84 patients with ALL after related (n = 46) or unrelated (n = 38) allogeneic SCT. Mean recipient age was 23 years (range: 1-60) and median follow-up was 18 months (range: 1-133). Forty-three patients were transplanted in CR1; 25 in CR2 or CR3; four were primary refractory; four in PR; eight in relapse. The conditioning regimen consisted of TBI/VP16/CY (n = 76), TBI/VP16 (n = 2), TBI/CY (n = 2), Bu/VP16/CY (n = 4). The OS at 3 years was 45% (44% unrelated, 46% related). Univariate analysis showed a significantly better OS for patients <18 years (P=0.03), mismatched sex-combination (P = 0.03), both with a stronger effect on increasing OS after unrelated SCT. Factors decreasing TRM were patient age <18 years (P = 0.004), patient CMV-seronegativity (P = 0.014), female recipient (P = 0.04). There was no significant difference in TRM and the relapse rate was similar in both donor type groups. Multivariate analysis showed that factors for increased OS which remained significant were mismatched sex-combination (RR: 0.70,95% CI: 0.51-0.93, P = 0.015), patient age < 18 years (RR: 0.66, 95% CI: 0.47-0.93, P = 0.016). A decreased TRM was found for female patients (RR: 0.56, 95% CI: 0.33-0.98, P=0.042), negative CMV status of the patient (RR: 0.57, 95% CI: 0.36-0.90, P = 0.015). Unrelated stem cell transplantation for high-risk ALL patients with no HLA-compatible family donor is justifiable.

  10. A unified association analysis approach for family and unrelated samples correcting for stratification.

    PubMed

    Zhu, Xiaofeng; Li, Shengchao; Cooper, Richard S; Elston, Robert C

    2008-02-01

    There are two common designs for association mapping of complex diseases: case-control and family-based designs. A case-control sample is more powerful to detect genetic effects than a family-based sample that contains the same numbers of affected and unaffected persons, although additional markers may be required to control for spurious association. When family and unrelated samples are available, statistical analyses are often performed in the family and unrelated samples separately, conditioning on parental information for the former, thus resulting in reduced power. In this report, we propose a unified approach that can incorporate both family and case-control samples and, provided the additional markers are available, at the same time corrects for population stratification. We apply the principal components of a marker matrix to adjust for the effect of population stratification. This unified approach makes it unnecessary to perform a conditional analysis of the family data and is more powerful than the separate analyses of unrelated and family samples, or a meta-analysis performed by combining the results of the usual separate analyses. This property is demonstrated in both a variety of simulation models and empirical data. The proposed approach can be equally applied to the analysis of both qualitative and quantitative traits.

  11. Comparable Outcomes after Nonmyeloablative Hematopoietic Cell Transplantation with Unrelated and Related Donors

    PubMed Central

    Mielcarek, Marco; Storer, Barry E.; Sandmaier, Brenda M.; Sorror, Mohamed L.; Maloney, David G.; Petersdorf, Effie; Martin, Paul J.; Storb, Rainer

    2007-01-01

    We sought to determine whether patients with hematologic malignancies treated by nonmyeloablative hematopoietic cell transplantation (HCT) at a single institution between December 1997 and June 2006 had worse outcomes with grafts from unrelated donors (n=184) as compared to HLA-identical related donors (n=221). The nonmyeloablative preparative regimen consisted of 2 Gy total body irradiation with (78%) or without (22%) fludarabine, and postgrafting mycophenolate mofetil and cyclosporine. After adjusting for HCT-comorbidity index, relapse risk, patient age, stem cell source, preparative regimen, prior CMV infection and sex-mismatch of donor and recipient in multivariate analysis, we found no statistically significant differences between unrelated and related HCT recipients in risks of non-relapse mortality (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.6-1.6; p=0.94), relapse (HR, 1.04; 95% CI, 0.7-1.5; p=0.82), or overall mortality (HR, 0.99; 95% CI, 0.7-1.4; p=0.94). Overall rates of severe acute and extensive chronic GVHD were also not significantly different between the two groups. We conclude that within the limitations of a retrospective study, these results indicate that candidates for nonmyeloablative HCT without suitable related donors may expect similar outcomes with grafts from unrelated donors. PMID:18022580

  12. Quantitating T Cell Cross-Reactivity for Unrelated Peptide Antigens1

    PubMed Central

    Ishizuka, Jeffrey; Grebe, Kristie; Shenderov, Eugene; Peters, Bjoern; Chen, Qiongyu; Peng, YanChun; Wang, Lili; Dong, Tao; Pasquetto, Valerie; Osroff, Carla; Sidney, John; Hickman, Heather; Cerundolo, Vincenzo; Sette, Alessandro; Bennink, Jack R.; McMchael, Andrew; Yewdell, Jonathan W.

    2009-01-01

    Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8+ T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8+ T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides (∼1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance. PMID:19734234

  13. Donor-derived 47, XXY in an unrelated cord blood transplant recipient.

    PubMed

    Kawaguchi, Kuniki; Nakamura, Takayuki; Nohara, Masayuki; Koteda, Satoko; Nomura, Kei; Morishige, Satoshi; Oku, Eijiro; Imamura, Rie; Mouri, Fumihiko; Seki, Ritsuko; Osaki, Koichi; Hashiguchi, Michitoshi; Yoshimoto, Kohji; Nagafuji, Koji; Okamura, Takashi

    2014-01-01

    A 65-year-old Japanese male with therapy-related myelodysplastic syndrome was admitted for unrelated cord blood transplantation. A cord blood unit from a male donor was obtained from the Japan Cord Blood Bank Network. The patient then received a conditioning regimen consisting of fludarabine, intravenous busulfan, and total body irradiation. Successful engraftment was obtained. The bone marrow examination on day 28 revealed trilineage engraftment, and chimerism analysis by variable number of tandem repeat polymerase chain reaction confirmed complete donor chimerism. At that time, conventional cytogenetics of the bone marrow aspirate showed 20 out of 20 metaphases with the 47, XXY karyotype characteristic of Klinefelter syndrome. Klinefelter syndrome is the most common genetic cause of human male infertility with a reported prevalence of 0.1-0.2% in the general population. In Japan Cord Blood Bank Network, there is no informed consent from parents about the possibility that post-unrelated cord blood transplantation patient evaluation may reveal donor-origin inherited diseases including cytogenetic abnormality. It is desirable to have opportunities in Japan discussing whether parents will be notified of the possibility that post-unrelated cord blood transplantation evaluation may reveal donor-derived illness incidentally. PMID:24555174

  14. Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body.

    PubMed

    Kang, Dawon; Wang, Jiaju; Hogan, James O; Vennekens, Rudi; Freichel, Marc; White, Carl; Kim, Donghee

    2014-05-01

    The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K(+) current and causes cell depolarization, Ca(2+) influx via voltage-dependent Ca(2+) channels and a rise in intracellular [Ca(2+)] ([Ca(2+)]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K(+) channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K(+), Na(+) and Cs(+) but not to Cl(-) or Ca(2+). The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca(2+) channel with FPL64176 activated the 20 pS channel when 1 mm Ca(2+) was present in the external solution. Ca(2+) (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca(2+)]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be -28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K(+) conductance and then activates a Na(+)-permeable, non-selective cation channel via depolarization-induced rise in [Ca(2+)]i. Our results suggest that inhibition of K(+) efflux and stimulation of Na(+) influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia.

  15. Combining non selective gas sensors on a mobile robot for identification and mapping of multiple chemical compounds.

    PubMed

    Bennetts, Victor Hernandez; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J; Marco, Santiago; Trincavelli, Marco

    2014-09-17

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources.

  16. Combining Non Selective Gas Sensors on a Mobile Robot for Identification and Mapping of Multiple Chemical Compounds

    PubMed Central

    Victor Hernandez, Bennetts; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J.; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources. PMID:25232911

  17. Nuclear accumulation of plasmid DNA can be enhanced by non-selective gating of the nuclear pore

    PubMed Central

    Vandenbroucke, Roosmarijn E.; Lucas, Bart; Demeester, Joseph; De Smedt, Stefaan C.; Sanders, Niek N.

    2007-01-01

    One of the major obstacles in non-viral gene transfer is the nuclear membrane. Attempts to improve the transport of DNA to the nucleus through the use of nuclear localization signals or importin-β have achieved limited success. It has been proposed that the nuclear pore complexes (NPCs) through which nucleocytoplasmic transport occurs are filled with a hydrophobic phase through which hydrophobic importins can dissolve. Therefore, considering the hydrophobic nature of the NPC channel, we evaluated whether a non-selective gating of nuclear pores by trans-cyclohexane-1,2-diol (TCHD), an amphipathic alcohol that reversibly collapses the permeability barrier of the NPCs, could be obtained and used as an alternative method to facilitate nuclear entry of plasmid DNA. Our data demonstrate for the first time that TCHD makes the nucleus permeable for both high molecular weight dextrans and plasmid DNA (pDNA) at non-toxic concentrations. Furthermore, in line with these observations, TCHD enhanced the transfection efficacy of both naked DNA and lipoplexes. In conclusion, based on the proposed structure of NPCs we succeeded to temporarily open the NPCs for macromolecules as large as pDNAs and demonstrated that this can significantly enhance non-viral gene delivery. PMID:17584788

  18. Combining non selective gas sensors on a mobile robot for identification and mapping of multiple chemical compounds.

    PubMed

    Bennetts, Victor Hernandez; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources. PMID:25232911

  19. Electrical Conductivity.

    ERIC Educational Resources Information Center

    Allen, Philip B.

    1979-01-01

    Examines Drude's classical (1900) theory of electrical conduction, details the objections to and successes of the 1900 theory, and investigates the Quantum (1928) theory of conduction, reviewing its successes and limitations. (BT)

  20. Antibodies to cardiac conducting tissue and abnormalities of cardiac conduction in rheumatoid arthritis.

    PubMed Central

    Villecco, A S; de Liberali, E; Bianchi, F B; Pisi, E

    1983-01-01

    The prevalence of antibodies to cardiac conducting tissue and cardiac conduction electrocardiographic abnormalities were studied in 60 patients with rheumatoid arthritis (RA). Complete or incomplete right bundle branch block (RBBB) was found in 21 patients (35%). Antibodies to cardiac conducting tissue were found in 16 (76%) of the 21 with RBBB and in eight (21%) of the 39 without RBBB. Cardiac conducting tissue antibodies (CCTA) were found only in one of 42 patients with RBBB unrelated to RA and in two out of 60 normal subjects. This newly documented immunological abnormality is thus correlated with disorder of conducting tissue. PMID:6352096

  1. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation

    PubMed Central

    Lee, Stephanie J.; Ahn, Kwang Woo; Spellman, Stephen; Wang, Hai-Lin; Aljurf, Mahmoud; Askar, Medhat; Dehn, Jason; Fernandez Viña, Marcelo; Gratwohl, Alois; Gupta, Vikas; Hanna, Rabi; Horowitz, Mary M.; Hurley, Carolyn K.; Inamoto, Yoshihiro; Kassim, Adetola A.; Nishihori, Taiga; Mueller, Carlheinz; Oudshoorn, Machteld; Petersdorf, Effie W.; Prasad, Vinod; Robinson, James; Saber, Wael; Schultz, Kirk R.; Shaw, Bronwen; Storek, Jan; Wood, William A.; Woolfrey, Ann E.; Anasetti, Claudio

    2014-01-01

    We examined current outcomes of unrelated donor allogeneic hematopoietic cell transplantation (HCT) to determine the clinical implications of donor-recipient HLA matching. Adult and pediatric patients who had first undergone myeloablative-unrelated bone marrow or peripheral blood HCT for acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome between 1999 and 2011 were included. All had high-resolution typing for HLA-A, -B, -C, and -DRB1. Of the total (n = 8003), cases were 8/8 (n = 5449), 7/8 (n = 2071), or 6/8 (n = 483) matched. HLA mismatch (6-7/8) conferred significantly increased risk for grades II to IV and III to IV acute graft vs host disease (GVHD), chronic GVHD, transplant-related mortality (TRM), and overall mortality compared with HLA-matched cases (8/8). Type (allele/antigen) and locus (HLA-A, -B, -C, and -DRB1) of mismatch were not associated with overall mortality. Among 8/8 matched cases, HLA-DPB1 and -DQB1 mismatch resulted in increased acute GVHD, and HLA-DPB1 mismatch had decreased relapse. Nonpermissive HLA-DPB1 allele mismatch was associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 8/8 (and 10/10) matched cases. Full matching at HLA-A, -B, -C, and -DRB1 is required for optimal unrelated donor HCT survival, and avoidance of nonpermissive HLA-DPB1 mismatches in otherwise HLA-matched pairs is indicated. PMID:25161269

  2. The impact of living-unrelated transplant on establishing deceased-donor liver program in Syria.

    PubMed

    Saeed, Bassam

    2014-10-01

    Liver transplant is the criterion standard for patients with end-stage liver disease. Yet there is no liver transplant in Syria. Traveling abroad for a liver transplant is a luxury few Syrians can afford. There is currently an on-going debate whether to start a liver transplant program using living or deceased donors. In 2003, a new law was enacted, authorizing the use of organs from volunteer strangers and deceased donors. Despite the positive aspects of this law (allowing unrelated donors to increase the number of transplants in the country); the negative aspects also were obvious. The poor used the law to sell their organs to the rich, and this model is in violation of the Istanbul Declaration. To better document transplant communities' perceptions on organ donation, an e-mail survey was sent to a nationally representative sample of physicians (n = 115) that showed that 58% of respondents did not support the start of liver transplant from live donors, as they fear a considerable risk for the donor and the recipient. Seventy-one percent of respondents believe that unrelated kidney donation has contributed to tarnishing the reputation of transplant, and 56% believe that a deceased-donor program can run in parallel with unrelated organ donations. The interest in deceased-donor program has been affected negatively by the systematic approach of using poor persons as the source of the organ. This lack of interest has affected starting a liver program that relies on deceased donors; especially the need for kidneys is more than livers. Health authorities in Syria were inclined to initiate a liver transplant program from live donors, despite the risks of serious morbidities and mortality. In conclusion then, paid kidney donation in actual effect is actually a hindrance to establishing a deceased-donor liver program.

  3. How to select the best available related or unrelated donor of hematopoietic stem cells?

    PubMed Central

    Tiercy, Jean-Marie

    2016-01-01

    Recognition of HLA incompatibilities by the immune system represents a major barrier to allogeneic hematopoietic stem cell transplantation. HLA genotypically identical sibling donors are, therefore, the gold standard for transplantation purposes, but only 30% patients have such a donor. For the remaining 70% patients alternative sources of stem cells are a matched unrelated adult volunteer donor, a haploidentical donor or a cord blood unit. The definition of ‘HLA matching’ depends on the level of resolution and on which loci are tested. The development of HLA molecular typing technologies and the availability of more than 27 million donors in the international database has greatly facilitated unrelated donor searches. The gold standard is high resolution typing at the HLA-A, -B, -C, -DRB1, and -DQB1 loci (10/10 match). Single disparities for HLA-A, -B, - C, or -DRB1 are associated with increased risk of post-transplant complications, but less so in patients with advanced disease, and in those undergoing T-cell-depleted allografting. HLA-DQB1 mismatches seem to be better tolerated and some HLA-C, -DRB1 and -DPB1 disparities are potentially less immunogenic. HLA typing by next-generation sequencing methods is likely to change matching algorithms by providing full sequence information on all HLA loci in a single step. In most European populations a 10/10 matched donor can be found for at least 50% of patients and an additional 20–30% patients may have a 9/10 matched donor. Genetic factors that help in identifying donors with less immunogenic mismatches are discussed. Haploidentical donors are increasingly used as an alternative source of stem cells for those patients lacking a matched unrelated donor. PMID:27252513

  4. Unrelated cord blood transplantation for patients with adult T-cell leukemia/lymphoma: experience at a single institute.

    PubMed

    Nakamura, Takayuki; Oku, Eijiro; Nomura, Kei; Morishige, Satoshi; Takata, Yuka; Seki, Ritsuko; Imamura, Rie; Osaki, Koichi; Hashiguchi, Michitoshi; Yakushiji, Kazuaki; Mouri, Fumihiko; Mizuno, Shinichi; Yoshimoto, Koji; Ohshima, Koichi; Nagafuji, Koji; Okamura, Takashi

    2012-11-01

    We report the results of unrelated cord blood transplantation (UCBT) for patients with adult T-cell leukemia/lymphoma (ATLL) conducted in our single institute. Ten patients with ATLL (nine acute and one lymphoma-type) received UCBT during the period from August 2003 to July 2011. The median age at the time of diagnosis of ATLL was 51 years (range 37-64). The median period from diagnosis of ATLL to UCBT was 130 days (range 94-344). Conditioning regimens were myeloablative for six and reduced intensity for four. The median number of infused nucleated cells and CD34 positive cells were 2.52 × 10(7)/kg and 1.04 × 10(5)/kg, respectively. There was no engraftment failure. Three patients developed grade II acute graft versus host disease, and four developed grade III. The estimated 2-year overall survival was 40 % (95 % CI 12-67 %). Four of six chemosensitive patients prior to UCBT survived for 1035, 793, 712, and 531 days post-UCBT, respectively. There were no survivors among the four chemorefractory patients prior to UCBT. Our data indicates that UCBT is feasible and provides long-term survival in patients with chemosensitive ATLL. PMID:22976114

  5. Obesity and the incidence of chronic diseases in Spain: a seemingly unrelated probit approach.

    PubMed

    Costa-Font, Joan; Gil, Joan

    2005-07-01

    Western societies can reduce avoidable mortality and morbidity by better understanding the relationship between obesity and chronic disease. This paper examines the empirical association between obesity and the incidence of heart disease, diabetes, hypertension, and elevated cholesterol. We analyze a broadly representative Spanish dataset, the 1999 Survey on Disabilities, Impairments and Health Status, using a health production theoretical framework together with a seemingly unrelated probit model approach that controls for unobserved heterogeneity and endogeneity. Its findings provide evidence of a positive and significant, although specification-dependent, association between obesity and the prevalence of all chronic illness examined.

  6. Three unrelated cases of paracentric inversions of 1p in individuals with abnormal phenotypes

    SciTech Connect

    Estop, A.M.; Karlin, S.M.; Wenger, S.L.; Steele, M.W.; Bansal, V.; Surti, U.; Lin, A.; Levinson, F.

    1994-02-15

    Paracentric inversions, involving a rearrangement within one chromosome arm, are rare. Although carriers of balanced paracentric inversions should theoretically not be at risk for abnormal offspring, such cases have been reported. The authors report on 2 unrelated cases of inherited paracentric inversions of 1p with breakpoints at p32 and p36.1 and p32.3 and p36.22 in individuals with abnormal phenotypes. Another case of 2 abnormal monozygotic twins with a de novo paracentric inversion of 1p with breakpoints at p22 and p34 is presented as well. 21 refs., 2 figs., 1 tab.

  7. Prognostic value of unrelated atypical serum immunofixation patterns during multiple myeloma therapy.

    PubMed

    Guimarães, Cristina; Bergantim, Rui; Ramalho, Renata; Couto, Nuno; Guimarães, João T; Trigo, Fernanda

    2012-06-26

    Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.

  8. Past and future of providing matched, unrelated donors for marrow transplantation.

    PubMed

    Roeckel, I E; Baker, J

    1997-01-01

    Prior to 1979, bone marrow transplants were only performed with histocompatible sibling donors. Once it was established that histocompatible, unrelated donors could donate marrow for transplantation, the recruitment of such donors needed to be standardized. Blood donor centers had already identified the histocompatibility locus antigen (HLA) typing for donors who could be recruited to donate bone marrow. Recruiting a large number of donors required systematic evaluation and testing according to defined standards which were published in 1988 by the National Marrow Donor Program (NMDP). Peripheral stem cell collection (PBS) has been added as a transplant source. It promises additional therapeutic modalities, such as gene splicing to address other than cancer therapy.

  9. Hemostatic alterations are unrelated to the stage of tumor in untreated malignant melanoma and breast carcinoma.

    PubMed

    Mannucci, P M; Vaglini, M; Maniezzo, M; Magni, E; Mari, D; Cascinelli, N

    1985-06-01

    A study of hemostatic variables was carried out in 80 untreated patients with breast adenocarcinoma or malignant melanoma, chosen as examples of tumors that can be accurately staged for localization or spread. The most marked abnormalities were high levels of clotting factors V and VIII, plasminogen, von Willebrand factor and fibrogen-fibrin degradation products. These abnormalities occurred in both types of tumors, albeit slightly more markedly in melanomas, and were also present in localized tumors. Our data indicate that in tumors, abnormalities of the hemostatic system are an early phenomenon unrelated to the presence of widespread malignancy.

  10. Scheduling Jobs with Variable Job Processing Times on Unrelated Parallel Machines

    PubMed Central

    Zhang, Guang-Qian; Wang, Jian-Jun; Liu, Ya-Jing

    2014-01-01

    m unrelated parallel machines scheduling problems with variable job processing times are considered, where the processing time of a job is a function of its position in a sequence, its starting time, and its resource allocation. The objective is to determine the optimal resource allocation and the optimal schedule to minimize a total cost function that dependents on the total completion (waiting) time, the total machine load, the total absolute differences in completion (waiting) times on all machines, and total resource cost. If the number of machines is a given constant number, we propose a polynomial time algorithm to solve the problem. PMID:24982933

  11. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

    PubMed

    Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

    2014-11-01

    Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

  12. Comparison of subtypes of Listeria monocytogenes isolates from naturally contaminated watershed samples using a combination of non-selective and selective enrichment methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two enrichment methods for Listeria monocytogenes using Immuno Magnetic Separation were tested to determine if they selected the same subtypes of isolates. Both methods included a non-selective enrichment and one included subculture in Fraser Broth. Naturally contaminated watershed samples from the ...

  13. Common genomic HLA haplotypes contributing to successful donor search in unrelated hematopoietic transplantation.

    PubMed

    Pedron, B; Duval, M; Elbou, O M; Moskwa, M; Jambou, M; Vilmer, E; Sterkers, G

    2003-03-01

    The aim of the study was to identify the most frequent HLA haplotypes in order to optimize donor searches in unrelated hematopoietic stem cell (HSC) transplantation. Pediatric patients from the north of France who underwent initial HLA typing for donor search in our center were included. Patients and family members were broadly typed for HLA class I and II. Patients were further DNA typed at the sequence level for HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles. In 200 of 207 patients HLA haplotypes were assigned by the mode of inheritance. The most common haplotypes were defined based on frequencies over 0.75%. Searches for unrelated donors were completed for 86 patients lacking a family donor. Matching criteria were either the optimal level of 10 alleles or a one-HLA class I mismatch as a second choice. Rates of successful search reach 85% for patients (n=20) who express at least one common five-allele (HLA-A/B/Cw/DRB1/DQB1) haplotype, but also 77% for more patients (n=53) who express at least one of the 20 most frequent three-allele (HLA-A/B/Cw) haplotypes. Success rates are clearly less (39%) in patients lacking these haplotypes. The use of these data to delineate search strategies is discussed.

  14. Knowledge and attitude of Lublin universities students' toward the opportunity of becoming unrelated bone marrow donor.

    PubMed

    Sikora, Agnieszka; Wiorkowski, Krzysztof; Szara, Paulina; Drabko, Katarzyna

    2014-01-01

    Hematopoietic Stem Cell Transplantation (HSCT) is a very important life-saving procedure to treat many disorders. In August 2014, there were more than 24.5 million donor registered in the Worldwide Bone Marrow Donor Register. In the Polish Register of Unrelated Bone Marrow and Umbilical Cord Blood Donors at the end of 2013 there were almost 540 thousand registered bone marrow donors. Despite increasing numbers of registered donors, the amount of requests also increased. It shows that the number of donors is still insufficient. The analysis of knowledge and attitude of Lublin universities students' toward the opportunity to become an unrelated bone marrow donor was the aim of our study. 1609 Lublin students from non-medical universities from different years and specializations of study, of both sexes, aged 19-35 took part in the survey. It consisted of 16 questions. There were knowledge-testing questions, and also personal ones. Among interviewees, 16% were registered as potential bone marrow donors. The reason for not being registered registration chosen most often was that the surveyed did not take this into consideration. Correct answers to all of the questions were given by 21% of students. The biggest number of incorrect answers was given to the question about a place from bone marrow is harvested - nearly 49%. Registered students showed a better level of knowledge than the unregistered. We noted a low level of knowledge about bone marrow donation and possibility of becoming potential bone marrow donor among Lublin universities students.

  15. Albright hereditary osteodystrophy and del(2)(q37.3) in four unrelated individuals

    SciTech Connect

    Phelan, M.C.; Rogers, R.C.; Clarkson, K.B.

    1995-07-31

    Albright hereditary osteodystrophy (AHO) is a condition with characteristic physical findings (short stature, obesity, round face, brachydactyly) but variable biochemical changes (pseudohypoparathyroidism, pseudopseudohypoparathyroidism). Most patients with AHO have decreased activity of the guanine nucleotide-binding protein (G{sub s} protein) that stimulates adenylyl cyclase. The gene encoding the a subunit of the G{sub s} protein (GNAS1) has been mapped to the long arm of chromosome 20. We describe 4 unrelated individuals with apparent AHO, associated with small terminal deletions of chromosome 2. All 4 patients had normal serum calcium levels consistent with pseudopseudohypoparathyroidism. Del(2)(q37) is the first consistent karyotypic abnormality that has been documented in AHO. The finding of the same small terminal deletion in 4 unrelated individuals with a similar phenotype suggests that a gene locus in the 2q37 region is important in the pathogenesis of Albright syndrome. The association of Albright syndrome and the GNAS1 locus on chromosome 20 is well documented. The observation of a second potential disease locus on chromosome 2 may help explain the heterogeneity observed in this disorder. 44 refs., 7 figs.

  16. Reproductive concessions between related and unrelated members promote eusociality in bees.

    PubMed

    Andrade, Aline C R; Miranda, Elder A; Del Lama, Marco A; Nascimento, Fábio S

    2016-05-23

    Animal societies exhibit remarkable variation in their breeding strategies. Individuals can maximize their fitness by either reproducing or by helping relatives. Social hymenopterans have been key taxa for the study of Hamilton's inclusive fitness theory because the haplodiploid sex-determination system results in asymmetric relatedness among breeders producing conflict over the partitioning of reproduction. In small cooperative groups of insects, totipotent individuals may maximize their inclusive fitness by controlling reproduction despotically rather than helping their relatives. Here, we demonstrate that the dominant females of the primitively eusocial bee Euglossa melanotricha (Apidae: Euglossini) control reproduction, but concede part of the reproductive output with their related and unrelated subordinates. As expected, a dominant female capitalizes on the direct reproduction of related subordinates, according to her interests. We found that reproductive skew was positively correlated with relatedness. The concessions were highly reduced in mother-daughter and sibling nests (relatedness r ± s.d. = 0.54 ± 0.02 and 0.79 ± 0.02, respectively) but much more egalitarian in unrelated associations (r = -0.10 ± 0.01). We concluded that reproductive skew in these primitively eusocial bees is strongly related to the genetic structure of associations, and also that females are able to assess pairwise relatedness, either directly or indirectly, and use this information to mediate social contracts.

  17. Reproductive concessions between related and unrelated members promote eusociality in bees.

    PubMed

    Andrade, Aline C R; Miranda, Elder A; Del Lama, Marco A; Nascimento, Fábio S

    2016-01-01

    Animal societies exhibit remarkable variation in their breeding strategies. Individuals can maximize their fitness by either reproducing or by helping relatives. Social hymenopterans have been key taxa for the study of Hamilton's inclusive fitness theory because the haplodiploid sex-determination system results in asymmetric relatedness among breeders producing conflict over the partitioning of reproduction. In small cooperative groups of insects, totipotent individuals may maximize their inclusive fitness by controlling reproduction despotically rather than helping their relatives. Here, we demonstrate that the dominant females of the primitively eusocial bee Euglossa melanotricha (Apidae: Euglossini) control reproduction, but concede part of the reproductive output with their related and unrelated subordinates. As expected, a dominant female capitalizes on the direct reproduction of related subordinates, according to her interests. We found that reproductive skew was positively correlated with relatedness. The concessions were highly reduced in mother-daughter and sibling nests (relatedness r ± s.d. = 0.54 ± 0.02 and 0.79 ± 0.02, respectively) but much more egalitarian in unrelated associations (r = -0.10 ± 0.01). We concluded that reproductive skew in these primitively eusocial bees is strongly related to the genetic structure of associations, and also that females are able to assess pairwise relatedness, either directly or indirectly, and use this information to mediate social contracts. PMID:27211350

  18. The effects of unrelated offspring whistle calls on capybaras (Hydrochoerus hydrochaeris).

    PubMed

    Dos Santos, E; Tokumaru, R S; Nogueira-Filho, S L G; Nogueira, S S C

    2014-08-01

    Parent-offspring vocal communication, such as the isolation call, is one of the essential adaptations in mammals that adjust parental responsiveness. Thus, our aim was to test the hypothesis that the function of the capybara infants' whistle is to attract conspecifics. We designed a playback experiment to investigate the reaction of 20 adult capybaras (seven males and 13 females) to pups' whistle calls - recorded from unrelated offspring - or to bird song, as control. The adult capybaras promptly responded to playback of unrelated pup whistles, while ignoring the bird vocalisation. The adult capybaras took, on average, 2.6 ± 2.5 seconds (s) to show a response to the whistles, with no differences between males and females. However, females look longer (17.0 ± 12.9 s) than males (3.0 ± 7.2 s) toward the sound source when playing the pups' whistle playback. The females also tended to approach the playback source, while males showed just a momentary interruption of ongoing behaviour (feeding). Our results suggest that capybara pups' whistles function as the isolation call in this species, but gender influences the intensity of the response.

  19. Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different Responses to Chemotherapy.

    PubMed

    Kasahara, Kohei; Onozawa, Masahiro; Miyashita, Naohiro; Yokohata, Emi; Yoshida, Miho; Kanaya, Minoru; Kosugi-Kanaya, Mizuha; Takemura, Ryo; Takahashi, Shojiro; Sugita, Junichi; Shigematsu, Akio; Takahata, Mutsumi; Fujisawa, Shinichi; Hashimoto, Daigo; Fujimoto, Katsuya; Endo, Tomoyuki; Kondo, Takeshi; Teshima, Takanori

    2016-01-01

    We report a case of acute myeloid leukemia (AML) with two cytogenetically unrelated clones. The patient was a 45-year-old male who was diagnosed with acute monoblastic leukemia (AMoL). Initial G-band analysis showed 51,XY,+6,+8,inv(9)(p12q13)c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis after induction therapy showed 45,XY,-7,inv(9)(p12q13)c[19]/46,XY,inv(9)(p12q13)c[1]. Retrospective FISH analysis revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with multiple trisomies was eliminated after induction therapy and never recurred, but a clone with monosomy 7 was still detected in myelodysplastic marrow with a normal blast percentage. Both clones were successfully eliminated after related peripheral blood stem cell transplantation, but the patient died of relapsed AML with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6, 8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with myelodysplasia-related changes(AML-MRC) with chromosome 7 monosomy showing different responses to chemotherapy. Simultaneous onset of cytogenetically unrelated hematological malignancies that each have a different disease status is a rare phenomenon but is important to diagnose for a correct understanding of the disease status and for establishing an appropriate treatment strategy. PMID:27034857

  20. Reproductive concessions between related and unrelated members promote eusociality in bees

    PubMed Central

    Andrade, Aline C. R.; Miranda, Elder A.; Del Lama, Marco A.; Nascimento, Fábio S.

    2016-01-01

    Animal societies exhibit remarkable variation in their breeding strategies. Individuals can maximize their fitness by either reproducing or by helping relatives. Social hymenopterans have been key taxa for the study of Hamilton’s inclusive fitness theory because the haplodiploid sex-determination system results in asymmetric relatedness among breeders producing conflict over the partitioning of reproduction. In small cooperative groups of insects, totipotent individuals may maximize their inclusive fitness by controlling reproduction despotically rather than helping their relatives. Here, we demonstrate that the dominant females of the primitively eusocial bee Euglossa melanotricha (Apidae: Euglossini) control reproduction, but concede part of the reproductive output with their related and unrelated subordinates. As expected, a dominant female capitalizes on the direct reproduction of related subordinates, according to her interests. We found that reproductive skew was positively correlated with relatedness. The concessions were highly reduced in mother-daughter and sibling nests (relatedness r ± s.d. = 0.54 ± 0.02 and 0.79 ± 0.02, respectively) but much more egalitarian in unrelated associations (r = −0.10 ± 0.01). We concluded that reproductive skew in these primitively eusocial bees is strongly related to the genetic structure of associations, and also that females are able to assess pairwise relatedness, either directly or indirectly, and use this information to mediate social contracts. PMID:27211350

  1. The effects of unrelated offspring whistle calls on capybaras (Hydrochoerus hydrochaeris).

    PubMed

    Dos Santos, E; Tokumaru, R S; Nogueira-Filho, S L G; Nogueira, S S C

    2014-08-01

    Parent-offspring vocal communication, such as the isolation call, is one of the essential adaptations in mammals that adjust parental responsiveness. Thus, our aim was to test the hypothesis that the function of the capybara infants' whistle is to attract conspecifics. We designed a playback experiment to investigate the reaction of 20 adult capybaras (seven males and 13 females) to pups' whistle calls - recorded from unrelated offspring - or to bird song, as control. The adult capybaras promptly responded to playback of unrelated pup whistles, while ignoring the bird vocalisation. The adult capybaras took, on average, 2.6 ± 2.5 seconds (s) to show a response to the whistles, with no differences between males and females. However, females look longer (17.0 ± 12.9 s) than males (3.0 ± 7.2 s) toward the sound source when playing the pups' whistle playback. The females also tended to approach the playback source, while males showed just a momentary interruption of ongoing behaviour (feeding). Our results suggest that capybara pups' whistles function as the isolation call in this species, but gender influences the intensity of the response. PMID:25627382

  2. Divalent cation permeability and blockade of Ca2+-permeant non-selective cation channels in rat adrenal zona glomerulosa cells

    PubMed Central

    Lotshaw, David P; Sheehan, Katherine A

    1999-01-01

    The effects of the divalent cations Ca2+, Mg2+ and Ni2+ on unitary Na+ currents through receptor-regulated non-selective cation channels were studied in inside-out and cell-attached patches from rat adrenal zona glomerulosa cells.External Ca2+ caused a concentration-dependent and voltage-independent inhibition of inward Na+ current, exhibiting an IC50 of 1.4 mm. The channel was also Ca2+ permeant and external Ca2+ shifted the reversal potential as expected for a channel exhibiting a constant Ca2+:Na+ permeability ratio near to 4.External and internal 2 mm Mg2+ caused voltage-dependent inhibition of inward and outward Na+ current, respectively. Modelling Mg2+ as an impermeant fast open channel blocker indicated that external Mg2+ blocked the pore at a single site exhibiting a zero voltage Kd of 5.1 mm for Mg2+ and located 19% of the distance through the transmembrane electric field from the external surface. Internal Mg2+ blocked the pore at a second site exhibiting a Kd of 1.7 mm for Mg2+ and located 36% of the distance through the transmembrane electric field from the cytosolic surface.External Ni2+ caused a voltage- and concentration-dependent slow blockade of inward Na+ current. Modelling Ni2+ as an impermeant slow open channel blocker indicated that Ni2+ blocked the pore at a single site exhibiting a Kd of 1.09 mm for Ni2+ and located 13.7% of the distance through the transmembrane electric field from the external surface.External 2 mm Mg2+ increased the Kd for external Ni2+ binding to 1.27 mm, consistent with competition for a single binding site. Changing ionic strength did not substantially affect Ni2+ blockade indicating the absence of surface potential under physiological ionic conditions.It is concluded that at least two divalent cation binding sites, separated by a high free energy barrier (the selectivity filter), are located in the pore and contribute to Ca2+ selectivity and permeability of the channel. PMID:9852322

  3. Cost effectiveness of etoricoxib versus celecoxib and non-selective NSAIDS in the treatment of ankylosing spondylitis.

    PubMed

    Jansen, Jeroen P; Gaugris, Sabine; Choy, Ernest H; Ostor, Andrew; Nash, Julian T; Stam, Wiro

    2010-01-01

    To evaluate the cost effectiveness of etoricoxib (90 mg/day) relative to celecoxib (200 or 400 mg/day), and the non-selective NSAIDs naproxen (1000 mg/day) and diclofenac (150 mg/day) in the initial treatment of ankylosing spondylitis (AS) from the UK NHS perspective. A Bayesian cost-effectiveness model was developed to estimate the costs and benefits associated with initiating AS treatment with etoricoxib, celecoxib, diclofenac or naproxen. Efficacy, safety and medical resource and cost data were obtained from the literature. The obtained efficacy estimates were synthesized with a mixed treatment comparison meta-analysis. Treatment benefit and degree of disease activity, as reflected with Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, were related to QALYs and AS-specific costs (related to BASDAI). Other cost outcomes related to drug acquisition, and gastrointestinal and cardiovascular safety. Uncertainty in the source data was translated into uncertainty in cost-effectiveness estimates and therefore decision uncertainty. Costs and outcomes were discounted at 3.5% per annum. There was a >98% probability that treatment with etoricoxib results in greater QALYs than the other interventions. Over a 30-year time horizon, starting AS treatment with etoricoxib was associated with about 0.4 more QALYs than the other interventions. At 2 years there was a 77% probability that etoricoxib had the lowest cost. This increased to >99% at 30 years. Etoricoxib is expected to save 13 620 UK pounds (year 2007 values) relative to celecoxib (200/400 mg), 9957 UK pounds relative to diclofenac and 9863 UK pounds relative to naproxen. For a willingness-to-pay ceiling ratio of 20 000 UK pounds per QALY, there was a >97% probability that etoricoxib was the most cost-effective treatment. Additional analysis with different assumptions, including celecoxib 200 mg, and ignoring cost-offsets associated with

  4. Effects of selective and non-selective glucocorticoid receptor II antagonists on rapid-onset diabetes in young rats.

    PubMed

    Beaudry, Jacqueline L; Dunford, Emily C; Teich, Trevor; Zaharieva, Dessi; Hunt, Hazel; Belanoff, Joseph K; Riddell, Michael C

    2014-01-01

    The blockade of glucocorticoid (GC) action through antagonism of the glucocorticoid receptor II (GRII) has been used to minimize the undesirable effects of chronically elevated GC levels. Mifepristone (RU486) is known to competitively block GRII action, but not exclusively, as it antagonizes the progesterone receptor. A number of new selective GRII antagonists have been developed, but limited testing has been completed in animal models of overt type 2 diabetes mellitus. Therefore, two selective GRII antagonists (C113176 and C108297) were tested to determine their effects in our model of GC-induced rapid-onset diabetes (ROD). Male Sprague-Dawley rats (∼ six weeks of age) were placed on a high-fat diet (60%), surgically implanted with pellets containing corticosterone (CORT) or wax (control) and divided into five treatment groups. Each group was treated with either a GRII antagonist or vehicle for 14 days after surgery: CORT pellets (400 mg/rat) + antagonists (80 mg/kg/day); CORT pellets + drug vehicle; and wax pellets (control) + drug vehicle. After 10 days of CORT treatment, body mass gain was increased with RU486 (by ∼20% from baseline) and maintained with C113176 administration, whereas rats given C108297 had similar body mass loss (∼15%) to ROD animals. Fasting glycemia was elevated in the ROD animals (>20 mM), normalized completely in animals treated with RU486 (6.2±0.1 mM, p<0.05) and improved in animals treated with C108297 and C113176 (14.0±1.6 and 8.8±1.6 mM, p<0.05 respectively). Glucose intolerance was normalized with RU486 treatment, whereas acute insulin response was improved with RU486 and C113176 treatment. Also, peripheral insulin resistance was attenuated with C113176 treatment along with improved levels of β-cell function while C108297 antagonism only provided modest improvements. In summary, C113176 is an effective agent that minimized some GC-induced detrimental metabolic effects and may provide an alternative to the effective, but non-selective

  5. Effects of Selective and Non-Selective Glucocorticoid Receptor II Antagonists on Rapid-Onset Diabetes in Young Rats

    PubMed Central

    Beaudry, Jacqueline L.; Dunford, Emily C.; Teich, Trevor; Zaharieva, Dessi; Hunt, Hazel; Belanoff, Joseph K.; Riddell, Michael C.

    2014-01-01

    The blockade of glucocorticoid (GC) action through antagonism of the glucocorticoid receptor II (GRII) has been used to minimize the undesirable effects of chronically elevated GC levels. Mifepristone (RU486) is known to competitively block GRII action, but not exclusively, as it antagonizes the progesterone receptor. A number of new selective GRII antagonists have been developed, but limited testing has been completed in animal models of overt type 2 diabetes mellitus. Therefore, two selective GRII antagonists (C113176 and C108297) were tested to determine their effects in our model of GC-induced rapid-onset diabetes (ROD). Male Sprague-Dawley rats (∼ six weeks of age) were placed on a high-fat diet (60%), surgically implanted with pellets containing corticosterone (CORT) or wax (control) and divided into five treatment groups. Each group was treated with either a GRII antagonist or vehicle for 14 days after surgery: CORT pellets (400 mg/rat) + antagonists (80 mg/kg/day); CORT pellets + drug vehicle; and wax pellets (control) + drug vehicle. After 10 days of CORT treatment, body mass gain was increased with RU486 (by ∼20% from baseline) and maintained with C113176 administration, whereas rats given C108297 had similar body mass loss (∼15%) to ROD animals. Fasting glycemia was elevated in the ROD animals (>20 mM), normalized completely in animals treated with RU486 (6.2±0.1 mM, p<0.05) and improved in animals treated with C108297 and C113176 (14.0±1.6 and 8.8±1.6 mM, p<0.05 respectively). Glucose intolerance was normalized with RU486 treatment, whereas acute insulin response was improved with RU486 and C113176 treatment. Also, peripheral insulin resistance was attenuated with C113176 treatment along with improved levels of β-cell function while C108297 antagonism only provided modest improvements. In summary, C113176 is an effective agent that minimized some GC-induced detrimental metabolic effects and may provide an alternative to the effective, but non-selective

  6. Electrical Conductivity.

    ERIC Educational Resources Information Center

    Hershey, David R.; Sand, Susan

    1993-01-01

    Explains how electrical conductivity (EC) can be used to measure ion concentration in solutions. Describes instrumentation for the measurement, temperature dependence and EC, and the EC of common substances. (PR)

  7. Nonmyeloablative Unrelated Donor Hematopoietic Cell Transplantation for the Treatment of Patients with Poor-Risk, Relapsed or Refractory Multiple Myeloma

    PubMed Central

    Georges, George E.; Maris, Michael B.; Maloney, David G.; Sandmaier, Brenda M.; Sorror, Mohamed L.; Shizuru, Judith A.; Niederwieser, Dietger W.; Agura, Edward D.; Bruno, Benedetto; McSweeney, Peter A.; Pulsipher, Michael A.; Chauncey, Thomas R.; Mielcarek, Marco; Storer, Barry E.; Storb, Rainer

    2007-01-01

    The purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation in patients with poor-risk multiple myeloma. Twenty-four patients were enrolled. Seventeen patients (71%) had chemotherapy-refractory disease and 14 patients (58%) had disease relapse or progression after prior autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43–135 days later with unrelated transplantation, while 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m2) and 2 Gray total body irradiation and human leukocyte antigen (HLA)-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced non-fatal graft rejection. The incidences of acute grades II, III and chronic graft-versus-host disease were 54%, 13% and 75%, respectively. The 3-year non-relapse mortality was 21%. Complete responses were observed in 10 patients (42%) and partial responses in 4 (17%). At 3 years, overall and progression-free survival rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior overall and progression-free survivals, 77% and 51%, compared to patients proceeding directly to unrelated donor transplantation, 44% and 11%, respectively (progression-free survival p-value, 0.03). In summary, for patients with poor-risk, relapsed or refractory multiple myeloma, cytoreductive autologous transplantation followed with nonmyeloablative conditioning and unrelated hematopoietic cell transplantation is effective treatment with low non-relapse mortality, high complete remission rates and prolonged disease-free survival. PMID:17287157

  8. Incestuous sisters: mate preference for brothers over unrelated males in Drosophila melanogaster.

    PubMed

    Loyau, Adeline; Cornuau, Jérémie H; Clobert, Jean; Danchin, Etienne

    2012-01-01

    The literature is full of examples of inbreeding avoidance, while recent mathematical models predict that inbreeding tolerance or even inbreeding preference should be expected under several realistic conditions like e.g. polygyny. We investigated male and female mate preferences with respect to relatedness in the fruit fly D. melanogaster. Experiments offered the choice between a first order relative (full-sibling or parent) and an unrelated individual with the same age and mating history. We found that females significantly preferred mating with their brothers, thus supporting inbreeding preference. Moreover, females did not avoid mating with their fathers, and males did not avoid mating with their sisters, thus supporting inbreeding tolerance. Our experiments therefore add empirical evidence for inbreeding preference, which strengthens the prediction that inbreeding tolerance and preference can evolve under specific circumstances through the positive effects on inclusive fitness.

  9. Temporally Unpredictable Sounds Exert a Context-Dependent Influence on Evaluation of Unrelated Images

    PubMed Central

    Bach, Dominik R.; Seifritz, Erich; Dolan, Raymond J.

    2015-01-01

    Temporally unpredictable stimuli influence murine and human behaviour, as previously demonstrated for sequences of simple sounds with regular or irregular onset. It is unknown whether this influence is mediated by an evaluation of the unpredictable sound sequences themselves, or by an interaction with task context. Here, we find that humans evaluate unrelated neutral pictures as more negative when these are presented together with a temporally unpredictable sound sequence, compared to a predictable sequence. The same is observed for evaluation of neutral, angry and fearful face photographs. Control experiments suggest this effect is specific to interspersed presentation of negative and neutral visual stimuli. Unpredictable sounds presented on their own were evaluated as more activating, but not more aversive, and were preferred over predictable sounds. When presented alone, these sound sequences also did not elicit tonic autonomic arousal or negative mood change. We discuss how these findings might account for previous data on the effects of unpredictable sounds, in humans and rodents. PMID:26098105

  10. Inhibitory spillover: increased urination urgency facilitates impulse control in unrelated domains.

    PubMed

    Tuk, Mirjam A; Trampe, Debra; Warlop, Luk

    2011-05-01

    Visceral states are known to reduce the ability to exert self-control. In the current research, we investigated how self-control is affected by a visceral factor associated with inhibition rather than with approach: bladder control. We designed four studies to test the hypothesis that inhibitory signals are not domain-specific but can spill over to unrelated domains, resulting in increased impulse control in the behavioral domain. In Study 1, participants' urination urgency correlated with performance on color-naming but not word-meaning trials of a Stroop task. In Studies 2 and 3, we found that higher levels of bladder pressure resulted in an increased ability to resist impulsive choices in monetary decision making. We found that inhibitory spillover effects are moderated by sensitivity of the Behavioral Inhibition System (Study 3) and can be induced by exogenous cues (Study 4). Implications for inhibition and impulse-control theories are discussed.

  11. Methanopyrus kandleri: an archaeal methanogen unrelated to all other known methanogens

    NASA Technical Reports Server (NTRS)

    Burggraf, S.; Stetter, K. O.; Rouviere, P.; Woese, C. R.

    1991-01-01

    Analysis of its 16S rRNA sequence shows that the newly discovered hyperthermophilic methanogen, Methanopryus kandleri, is phylogenetically unrelated to any other known methanogen. The organism represents a separate lineage originating near the root of the archaeal tree. Although the 16S rRNA sequence of Mp. kandleri resembles euryarchaeal 16S rRNAs more than it does crenarchaeal, it shows more crenarchaeal signature features than any known euryarchaeal rRNA. Attempts to place it in relation to the root of the archaeal tree show that the Mp. kandleri lineage likely arises from the euryarchaeal branch of the tree. While the existence of so deeply branching a methanogenic lineage brings into question the thesis that methanogenesis evolved from an earlier metabolism similar to that seen in Thermococcus, it at the same time reinforces the notion that the aboriginal [correction of aborginal] archaeon was a thermophile.

  12. Symptomatic female heterozygotes for adrenoleukodystrophy: A report of two unrelated cases and review of the literature.

    PubMed

    O'Brien, T J; Gates, P G; Byrne, E

    1996-04-01

    We report two cases of unrelated female heterozygotes for adrenoleukodystrophy (ALD) who have developed progressive neurological disease. Both presented with a progressive myelopathy in midlife and one has since also developed a peripheral neuropathy. Both women had elevated very long chain fatty acid (VLCFA) levels. One patient has been on Lorenzo's oil for 2 years with normalisation of her plasma VLCFA assays but her condition has progressed relentlessly and the second discontinued Lorenzo's oil after 1 month due to unacceptable weight loss. Review of the literature reveals that significant neurological symptoms develop in 15-20% of female heterozygotes and that abnormalities on neurological examination occur in up to 55%. Despite a not excessively rare estimated gene frequency of 1 20,000 the diagnosis of a symptomatic heterozygote for ALD is rarely made in the absence of an affected male relative with most patients misdiagnosed as suffering from multiple sclerosis.

  13. Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia.

    PubMed

    Yunis, Juan J; Yunis, Emilio J

    2013-09-01

    The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest.

  14. Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

    PubMed Central

    Yunis, Juan J.; Yunis, Emilio J.

    2013-01-01

    The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest. PMID:24130438

  15. A case of Schizophyllum commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia.

    PubMed

    Toya, Takashi; Shinohara, Akihito; Tatsuno, Keita; Seo, Sachiko; Nannya, Yasuhito; Ichikawa, Motoshi; Makimura, Koichi; Moriya, Kyoji; Kurokawa, Mineo

    2013-08-01

    Schizophyllum commune is a globally distributed basidiomycete fungus that is known as a rare cause of sinusitis, for which no prompt treatment has been established. We describe the first report of S. commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia. Thirteen days after transplantation, a 23-year-old female developed maxillary and ethmoid sinusitis. The sinusitis was antimicrobial-resistant, and the sinus aspirate culture revealed white wooly mold, which was identified as S. commune by nucleotide sequencing. The patient was successfully treated with intravenous administration of liposomal amphotericin B for 2 months, followed by oral voriconazole. This report suggests the effectiveness of liposomal amphotericin B and voriconazole for S. commune infection in immunocompromised patients. Given the difficulty in distinguishing S. commune infection from aspergillosis by standard culture methods, the incidence of S. commune infection following allogeneic hematopoietic stem cell transplantation may be underestimated. Nucleotide sequencing may be useful in the diagnosis of S. commune infection.

  16. Mutualistic Benefits Generate an Unequal Distribution of Risky Activities Among Unrelated Group Members

    NASA Astrophysics Data System (ADS)

    Kukuk, Penelope F.; Ward, Seamus A.; Jozwiak, Amy

    Recent studies provide a new challenge to the adequacy of theories concerning the evolution of cooperation among nonrelatives: some individuals perform high-risk activities while others do not. We examined a communal hymenopteran species, Lasioglossum(Chilalictus)hemichalceum, to determine why group members engaged in demonstrably risky activities (foraging) tolerate the selfish behavior (remaining in the nest) of unrelated nestmates. Experimental removal of adult females indicated that their presence is required for the protection of brood from ant predators. Nonforagers ensure the continued presence of adults in the nest if the risk-taking foragers die, thereby safeguarding the survival of forager offspring. This results in an unequal distribution of risky activities within social groups in which avoidance of risky activities by some group members is ultimately beneficial to risk takers.

  17. Incestuous Sisters: Mate Preference for Brothers over Unrelated Males in Drosophila melanogaster

    PubMed Central

    Loyau, Adeline; Cornuau, Jérémie H.; Clobert, Jean; Danchin, Étienne

    2012-01-01

    The literature is full of examples of inbreeding avoidance, while recent mathematical models predict that inbreeding tolerance or even inbreeding preference should be expected under several realistic conditions like e.g. polygyny. We investigated male and female mate preferences with respect to relatedness in the fruit fly D. melanogaster. Experiments offered the choice between a first order relative (full-sibling or parent) and an unrelated individual with the same age and mating history. We found that females significantly preferred mating with their brothers, thus supporting inbreeding preference. Moreover, females did not avoid mating with their fathers, and males did not avoid mating with their sisters, thus supporting inbreeding tolerance. Our experiments therefore add empirical evidence for inbreeding preference, which strengthens the prediction that inbreeding tolerance and preference can evolve under specific circumstances through the positive effects on inclusive fitness. PMID:23251487

  18. Inhibitory spillover: increased urination urgency facilitates impulse control in unrelated domains.

    PubMed

    Tuk, Mirjam A; Trampe, Debra; Warlop, Luk

    2011-05-01

    Visceral states are known to reduce the ability to exert self-control. In the current research, we investigated how self-control is affected by a visceral factor associated with inhibition rather than with approach: bladder control. We designed four studies to test the hypothesis that inhibitory signals are not domain-specific but can spill over to unrelated domains, resulting in increased impulse control in the behavioral domain. In Study 1, participants' urination urgency correlated with performance on color-naming but not word-meaning trials of a Stroop task. In Studies 2 and 3, we found that higher levels of bladder pressure resulted in an increased ability to resist impulsive choices in monetary decision making. We found that inhibitory spillover effects are moderated by sensitivity of the Behavioral Inhibition System (Study 3) and can be induced by exogenous cues (Study 4). Implications for inhibition and impulse-control theories are discussed. PMID:21467548

  19. Can a near win kindle motivation? The impact of nearly winning on motivation for unrelated rewards.

    PubMed

    Wadhwa, Monica; Kim, JeeHye Christine

    2015-06-01

    Common intuition and research suggest that winning is more motivating than losing. However, we propose that just failing to obtain a reward (i.e., nearly winning it) in one task leads to broader, positive motivational effects on subsequent unrelated tasks relative to clearly losing or actually obtaining the reward. We manipulated a near-win experience using a game app in Experiments 1 through 3 and a lottery in Experiment 4. Our findings showed that nearly winning in one task subsequently led participants to walk faster to get to a chocolate bar (Experiment 1), salivate more for money (Experiment 2), and increase their effort to earn money in a card-sorting task (Experiment 3). A field study (Experiment 4) demonstrated that nearly winning led people to subsequently spend more money on desirable consumer products. Finally, our findings showed that when the activated motivational state was dampened in an intervening task, the nearly-winning effect was attenuated.

  20. Can a near win kindle motivation? The impact of nearly winning on motivation for unrelated rewards.

    PubMed

    Wadhwa, Monica; Kim, JeeHye Christine

    2015-06-01

    Common intuition and research suggest that winning is more motivating than losing. However, we propose that just failing to obtain a reward (i.e., nearly winning it) in one task leads to broader, positive motivational effects on subsequent unrelated tasks relative to clearly losing or actually obtaining the reward. We manipulated a near-win experience using a game app in Experiments 1 through 3 and a lottery in Experiment 4. Our findings showed that nearly winning in one task subsequently led participants to walk faster to get to a chocolate bar (Experiment 1), salivate more for money (Experiment 2), and increase their effort to earn money in a card-sorting task (Experiment 3). A field study (Experiment 4) demonstrated that nearly winning led people to subsequently spend more money on desirable consumer products. Finally, our findings showed that when the activated motivational state was dampened in an intervening task, the nearly-winning effect was attenuated. PMID:25940671

  1. Allelic barley MLA immune receptors recognize sequence-unrelated avirulence effectors of the powdery mildew pathogen

    PubMed Central

    Lu, Xunli; Kracher, Barbara; Saur, Isabel M. L.; Bauer, Saskia; Ellwood, Simon R.; Wise, Roger; Yaeno, Takashi; Maekawa, Takaki; Schulze-Lefert, Paul

    2016-01-01

    Disease-resistance genes encoding intracellular nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are key components of the plant innate immune system and typically detect the presence of isolate-specific avirulence (AVR) effectors from pathogens. NLR genes define the fastest-evolving gene family of flowering plants and are often arranged in gene clusters containing multiple paralogs, contributing to copy number and allele-specific NLR variation within a host species. Barley mildew resistance locus a (Mla) has been subject to extensive functional diversification, resulting in allelic resistance specificities each recognizing a cognate, but largely unidentified, AVRa gene of the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We applied a transcriptome-wide association study among 17 Bgh isolates containing different AVRa genes and identified AVRa1 and AVRa13, encoding candidate-secreted effectors recognized by Mla1 and Mla13 alleles, respectively. Transient expression of the effector genes in barley leaves or protoplasts was sufficient to trigger Mla1 or Mla13 allele-specific cell death, a hallmark of NLR receptor-mediated immunity. AVRa1 and AVRa13 are phylogenetically unrelated, demonstrating that certain allelic MLA receptors evolved to recognize sequence-unrelated effectors. They are ancient effectors because corresponding loci are present in wheat powdery mildew. AVRA1 recognition by barley MLA1 is retained in transgenic Arabidopsis, indicating that AVRA1 directly binds MLA1 or that its recognition involves an evolutionarily conserved host target of AVRA1. Furthermore, analysis of transcriptome-wide sequence variation among the Bgh isolates provides evidence for Bgh population structure that is partially linked to geographic isolation. PMID:27702901

  2. Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation.

    PubMed

    MacMillan, Margaret L; Radloff, Gretchen A; DeFor, Todd E; Weisdorf, Daniel J; Davies, Stella M

    2003-05-01

    The interleukin 1 (IL-1) gene family includes three members (IL-1-alpha, IL-1-beta and IL-1Ra) that mediate immune and inflammatory responses through two specific cell surface receptors. Cytosine to thymine transitions at codons -889 and -511 in the IL-1-alpha and IL-1-beta genes, respectively, and an 86-base pair repeat in the IL-1Ra are believed to influence gene transcription. We have genotyped these three polymorphisms in 90 donor/recipient pairs undergoing unrelated donor bone marrow transplantation (BMT) at the University of Minnesota. We found no association between the occurrence of acute GVHD and donor and/or recipient polymorphisms of any of the three IL-1 genes. The presence of at least one IL-1alpha- 889 T allele in the donor was associated with significantly improved survival in univariate analysis (survival at 1 year 40% C/C donor, 68% T/C donor, 75% T/T donor, P < 0.01). Multiple regression analysis showed that if the donor and recipient each possessed the IL-1alpha T allele there was significantly improved survival [relative risk (RR) 0.2, P < 0.01] and decreased treatment-related mortality (TRM; RR 0.2, P = 0.01). The presence of the IL-1beta T allele in donor and recipient was also associated with improved survival (RR 0.2, P < 0.01) and decreased TRM (RR 0.1, P < 0.01). These data suggest that donor polymorphism in IL-1alpha and IL-1beta might influence survival after unrelated donor BMT, but does not alter risk of GVHD.

  3. Elevated plasma oxytocin levels in children with Prader-Willi syndrome compared with healthy unrelated siblings.

    PubMed

    Johnson, Lisa; Manzardo, Ann M; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

    2016-03-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder associated with distinct abnormal behaviors including hyperphagia, profound social deficits, and obsessive-compulsive tendencies. PWS males showed reduced oxytocin receptor (OTR) gene expression and density in the hypothalamic paraventricular nucleus that may play a role in PWS psychopathology. Oxytocin is an anorexigenic neuropeptide similar to vasopressin that is associated with social cognition and obsessive-compulsive behavior. To evaluate oxytocin biology in PWS, we examined overnight fasting plasma oxytocin levels in 23 children with PWS (mean ± SD age: 8.2 ± 2.0 year) having genetic confirmation and 18 age matched healthy unrelated siblings without PWS (mean ± SD age: 8.2 ± 2.3 year) and a similar gender ratio under the same clinical assessments, specimen processing and laboratory conditions. Multiplex immune assays were carried out using the Milliplex Human Neuropeptide Magnetic panel and the Luminex system. Natural log-transformed oxytocin levels were analyzed using general linear model adjusting for diagnosis, gender, age and body mass index (BMI). Oxytocin plasma levels were significantly elevated in children with PWS (168 ± 121 pg/ml) compared with unrelated and unaffected siblings without the diagnosis of PWS (64.8 ± 83.8 pg/ml, F = 8.8, P < 0.01) and the diagnosis of PWS predicted oxytocin level (F = 9.5, P < 0.003) in controlled regression analysis with an overall model fit R(2) = 0.33 (P < 0.01). The symptoms of hyperphagia, anxiety and repetitive behaviors classically seen in PWS may be related to the disruption of oxytocin responsivity or feedback in the hypothalamic paraventricular nucleus possibly influencing vasopressin signaling. Further study is needed to characterize oxytocin function in PWS. PMID:26615966

  4. Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT.

    PubMed

    Crivello, Pietro; Heinold, Andreas; Rebmann, Vera; Ottinger, Hellmut D; Horn, Peter A; Beelen, Dietrich W; Fleischhauer, Katharina

    2016-07-01

    The role of HLA amino acid (AA) polymorphism for the outcome of hematopoietic cell transplantation (HCT) is controversial, in particular for HLA class II. Here, we investigated this question in nonpermissive HLA-DPB1 T-cell epitope (TCE) mismatches reflected by numerical functional distance (FD) scores, assignable to all HLA-DPB1 alleles based on the combined impact of 12 polymorphic AAs. We calculated the difference in FD scores (ΔFD) of mismatched HLA-DPB1 alleles in patients and their 10/10 HLA-matched unrelated donors of 379 HCTs performed at our center for acute leukemia or myelodysplastic syndrome. Receiver-operator curve-based stratification into 2 ΔFD subgroups showed a significantly higher percentage of nonpermissive TCE mismatches for ΔFD >2.665, compared with ΔFD ≤2.665 (88% vs 25%, P < .0001). In multivariate analysis, ΔFD >2.665 was significantly associated with overall survival (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.05-1.87; P < .021) and event-free survival (HR, 1.39; 95% CI, 1.05-1.82; P < .021), compared with ΔFD ≤2.665. These associations were stronger than those observed for TCE mismatches. There was a marked but not statistically significant increase in the hazards of relapse and nonrelapse mortality in the high ΔFD subgroup, whereas no differences were observed for acute and chronic graft-versus-host disease. Seven nonconservative AA substitutions in peptide-binding positions had a significantly stronger impact on ΔFD compared with 5 others (P = .0025), demonstrating qualitative differences in the relative impact of AA polymorphism in HLA-DPB1. The novel concept of ΔFD sheds new light onto nonpermissive HLA-DPB1 mismatches in unrelated HCT. PMID:27162243

  5. Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs.

    PubMed

    Gerstenfeld, Louis C; Thiede, Mark; Seibert, Karen; Mielke, Cindy; Phippard, Deborah; Svagr, Bohus; Cullinane, Dennis; Einhorn, Thomas A

    2003-07-01

    . Histological analysis at 21 days showed that the calluses in the ketorolac-treated group contained substantial amounts of residual cartilage while neither the control nor the parecoxib-treated animals showed comparable amounts of cartilage at this stage. These results demonstrate that ketorolac and parecoxib delay fracture healing in this model, but in this study daily administration of ketorolac, a non-selective COX inhibitor had a greater affect on this process. They further demonstrate that a COX-2 selective NSAID, such as parecoxib (valdecoxib), has only a small effect on delaying fracture healing even at doses that are known to fully inhibit prostaglandin production.

  6. Appropriate Conduct

    ERIC Educational Resources Information Center

    Di Lullo, Louis

    2004-01-01

    Many years ago when the author assumed the role of assistant principal for school climate, discipline, and attendance, he inherited many school policies and guidelines that were outdated, unfair, and without merit in the current school climate. Because the school conduct code had not been revised since the school opened in 1960, many of the…

  7. Potential roles of the interaction between model V1 neurons with orientation-selective and non-selective surround inhibition in contour detection

    PubMed Central

    Yang, Kai-Fu; Li, Chao-Yi; Li, Yong-Jie

    2015-01-01

    Both the neurons with orientation-selective and with non-selective surround inhibition have been observed in the primary visual cortex (V1) of primates and cats. Though the inhibition coming from the surround region (named as non-classical receptive field, nCRF) has been considered playing critical role in visual perception, the specific role of orientation-selective and non-selective inhibition in the task of contour detection is less known. To clarify above question, we first carried out computational analysis of the contour detection performance of V1 neurons with different types of surround inhibition, on the basis of which we then proposed two integrated models to evaluate their role in this specific perceptual task by combining the two types of surround inhibition with two different ways. The two models were evaluated with synthetic images and a set of challenging natural images, and the results show that both of the integrated models outperform the typical models with orientation-selective or non-selective inhibition alone. The findings of this study suggest that V1 neurons with different types of center–surround interaction work in cooperative and adaptive ways at least when extracting organized structures from cluttered natural scenes. This work is expected to inspire efficient phenomenological models for engineering applications in field of computational machine-vision. PMID:26136664

  8. Electrodeless conductivity.

    PubMed

    Light, T S; McHale, E J; Fletcher, K S

    1989-01-01

    Electrodeless conductivity is a technique for measuring the concentration of electrolytes in solution and utilizes a probe consisting of two toroids in close proximity, both of which are immersed in the solution. In special cases, the toroids may be mounted externally on insulated pipes carrying the solution. One toroid radiates an alternating electric field in the audiofrequency range and the other acts as a receiver to pick up the small current induced by the ions moving in a conducting loop of solution. Coatings which would foul contacting electrodes, such as suspensions, precipitates or oil, have little or no effect. Applications are chiefly to continuous measurement in the chemical processing industries, including pulp and paper, mining and heavy chemical production. The principles and practical details of the method are reviewed and cell-diameter, wall, and temperature effects are discussed. PMID:18964695

  9. Conductive Polymers

    SciTech Connect

    Bohnert, G.W.

    2002-11-22

    Electroluminescent devices such as light-emitting diodes (LED) and high-energy density batteries. These new polymers offer cost savings, weight reduction, ease of processing, and inherent rugged design compared to conventional semiconductor materials. The photovoltaic industry has grown more than 30% during the past three years. Lightweight, flexible solar modules are being used by the U.S. Army and Marine Corps for field power units. LEDs historically used for indicator lights are now being investigated for general lighting to replace fluorescent and incandescent lights. These so-called solid-state lights are becoming more prevalent across the country since they produce efficient lighting with little heat generation. Conductive polymers are being sought for battery development as well. Considerable weight savings over conventional cathode materials used in secondary storage batteries make portable devices easier to carry and electric cars more efficient and nimble. Secondary battery sales represent an $8 billion industry annually. The purpose of the project was to synthesize and characterize conductive polymers. TRACE Photonics Inc. has researched critical issues which affect conductivity. Much of their work has focused on production of substituted poly(phenylenevinylene) compounds. These compounds exhibit greater solubility over the parent polyphenylenevinylene, making them easier to process. Alkoxy substituted groups evaluated during this study included: methoxy, propoxy, and heptyloxy. Synthesis routes for production of alkoxy-substituted poly phenylenevinylene were developed. Considerable emphasis was placed on final product yield and purity.

  10. Tumor-Unrelated CD4 T Cell Help Augments CD134 plus CD137 Dual Costimulation Tumor Therapy.

    PubMed

    Mittal, Payal; St Rose, Marie-Clare; Wang, Xi; Ryan, Joseph M; Wasser, Jeffrey S; Vella, Anthony T; Adler, Adam J

    2015-12-15

    The ability of immune-based cancer therapies to elicit beneficial CD8(+) CTLs is limited by tolerance pathways that inactivate tumor-specific CD4 Th cells. A strategy to bypass this problem is to engage tumor-unrelated CD4 Th cells. Thus, CD4 T cells, regardless of their specificity per se, can boost CD8(+) CTL priming as long as the cognate epitopes are linked via presentation on the same dendritic cell. In this study, we assessed the therapeutic impact of engaging tumor-unrelated CD4 T cells during dual costimulation with CD134 plus CD137 that provide help via the above-mentioned classical linked pathway, as well as provide nonlinked help that facilitates CTL function in T cells not directly responding to cognate Ag. We found that engagement of tumor-unrelated CD4 Th cells dramatically boosted the ability of dual costimulation to control the growth of established B16 melanomas. Surprisingly, this effect depended upon a CD134-dependent component that was extrinsic to the tumor-unrelated CD4 T cells, suggesting that the dual costimulated helper cells are themselves helped by a CD134(+) cell(s). Nevertheless, the delivery of therapeutic help tracked with an increased frequency of tumor-infiltrating granzyme B(+) effector CD8 T cells and a reciprocal decrease in Foxp3(+)CD4(+) cell frequency. Notably, the tumor-unrelated CD4 Th cells also infiltrated the tumors, and their deletion several days following initial T cell priming negated their therapeutic impact. Taken together, dual costimulation programs tumor-unrelated CD4 T cells to deliver therapeutic help during both the priming and effector stages of the antitumor response.

  11. Tumor-Unrelated CD4 T Cell Help Augments CD134 plus CD137 Dual Costimulation Tumor Therapy.

    PubMed

    Mittal, Payal; St Rose, Marie-Clare; Wang, Xi; Ryan, Joseph M; Wasser, Jeffrey S; Vella, Anthony T; Adler, Adam J

    2015-12-15

    The ability of immune-based cancer therapies to elicit beneficial CD8(+) CTLs is limited by tolerance pathways that inactivate tumor-specific CD4 Th cells. A strategy to bypass this problem is to engage tumor-unrelated CD4 Th cells. Thus, CD4 T cells, regardless of their specificity per se, can boost CD8(+) CTL priming as long as the cognate epitopes are linked via presentation on the same dendritic cell. In this study, we assessed the therapeutic impact of engaging tumor-unrelated CD4 T cells during dual costimulation with CD134 plus CD137 that provide help via the above-mentioned classical linked pathway, as well as provide nonlinked help that facilitates CTL function in T cells not directly responding to cognate Ag. We found that engagement of tumor-unrelated CD4 Th cells dramatically boosted the ability of dual costimulation to control the growth of established B16 melanomas. Surprisingly, this effect depended upon a CD134-dependent component that was extrinsic to the tumor-unrelated CD4 T cells, suggesting that the dual costimulated helper cells are themselves helped by a CD134(+) cell(s). Nevertheless, the delivery of therapeutic help tracked with an increased frequency of tumor-infiltrating granzyme B(+) effector CD8 T cells and a reciprocal decrease in Foxp3(+)CD4(+) cell frequency. Notably, the tumor-unrelated CD4 Th cells also infiltrated the tumors, and their deletion several days following initial T cell priming negated their therapeutic impact. Taken together, dual costimulation programs tumor-unrelated CD4 T cells to deliver therapeutic help during both the priming and effector stages of the antitumor response. PMID:26561553

  12. Could living unrelated renal transplantation ameliorate the actual shortage of organs in the Balkan region?

    PubMed Central

    Rambabova-Busljetic, I; Popov, Z; Masin-Spasovska, j; Sikole, A; Selim, Gj; Dohcev, S; Ivanovski, N

    2013-01-01

    Background: Despite the efforts for more transplants performed with organs from deceased donors, the living renal transplantation is still the predominant transplant activity in the Balkan region. In order to adress the severe organ shortage, we started accepting unrelated (emotionally related) living donors (LURD). Here we present our 10-year experience with living unrelated renal transplantation (LURT). Methods: Twenty four LURT were performed in our center in the last 10 years. The mean recipients and donors age was 41.7 and 47.2 years, respectively. As LURD spouses (n=17) and extended family members (n=7) were accepted predominantly. All donors went through careful psychological evaluation in order to confirm emotional relationship. The final decision was taken after both the recipient and the donor signed a consent in front of a judge. A quadruple sequential immunosuppressive protocol was used in all recipients. The 5-year Kaplan Meier graft survival rate, HLA mismatch, rejection episodes, delayed graft function, serum creatinine and Glomerular filtration rate-Modification of the diet in renal disease (GFR-MDRD) were analyzed. The results were compared with 30 living related renal transplants (LRT) performed during the same time with mean recipients and donors age of 35.9 and 58.5 years, respectively. Results: The mean follow up for LURT and LRT recipients were 81.4 and 79.6 months, respectively. There was a significant difference regarding recipients and donors age, HLA mismatch (5.07 and 2.9) and rejection episodes (16% vs. 11%) in LURT and LRT recipients. The 5 years graft survival rate was excellent in both groups (83 and 81%, respectively). There was no significant difference in 5 years serum creatinine (129.3 vs 121.1 μmol/lit) and 5 years GFR-MDRD (56.6 and 58.6 ml/min). Conclusion: The authors present an excellent 5-year graft survival rate in both LURT and LRT recipients. Therefore, LURT could ameliorate the severe organ shortage in the region and

  13. Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.

    PubMed

    Georges, George E; Maris, Michael; Sandmaier, Brenda M; Malone, David G; Feinstein, Lyle; Niederweiser, Dietger; Shizuru, Judith A; McSweeney, Peter A; Chauncey, Thomas R; Agura, Edward; Little, Marie-Trse; Sahebi, Firoozeh; Hegenbart, Ute; Pulsipher, Michael A; Bruno, Benedetto; Forman, Stephen; Woolfrey, Ann E; Radich, Jerald P; Blume, Karl G; Storb, Rainer

    2002-08-01

    Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred

  14. Two Unrelated 8-Vinyl Reductases Ensure Production of Mature Chlorophylls in Acaryochloris marina

    PubMed Central

    Chen, Guangyu E.; Hitchcock, Andrew; Jackson, Philip J.; Chaudhuri, Roy R.; Dickman, Mark J.; Hunter, C. Neil

    2016-01-01

    ABSTRACT The major photopigment of the cyanobacterium Acaryochloris marina is chlorophyll d, while its direct biosynthetic precursor, chlorophyll a, is also present in the cell. These pigments, along with the majority of chlorophylls utilized by oxygenic phototrophs, carry an ethyl group at the C-8 position of the molecule, having undergone reduction of a vinyl group during biosynthesis. Two unrelated classes of 8-vinyl reductase involved in the biosynthesis of chlorophylls are known to exist, BciA and BciB. The genome of Acaryochloris marina contains open reading frames (ORFs) encoding proteins displaying high sequence similarity to BciA or BciB, although they are annotated as genes involved in transcriptional control (nmrA) and methanogenesis (frhB), respectively. These genes were introduced into an 8-vinyl chlorophyll a-producing ΔbciB strain of Synechocystis sp. strain PCC 6803, and both were shown to restore synthesis of the pigment with an ethyl group at C-8, demonstrating their activities as 8-vinyl reductases. We propose that nmrA and frhB be reassigned as bciA and bciB, respectively; transcript and proteomic analysis of Acaryochloris marina reveal that both bciA and bciB are expressed and their encoded proteins are present in the cell, possibly in order to ensure that all synthesized chlorophyll pigment carries an ethyl group at C-8. Potential reasons for the presence of two 8-vinyl reductases in this strain, which is unique for cyanobacteria, are discussed. IMPORTANCE The cyanobacterium Acaryochloris marina is the best-studied phototrophic organism that uses chlorophyll d for photosynthesis. Unique among cyanobacteria sequenced to date, its genome contains ORFs encoding two unrelated enzymes that catalyze the reduction of the C-8 vinyl group of a precursor molecule to an ethyl group. Carrying a reduced C-8 group may be of particular importance to organisms containing chlorophyll d. Plant genomes also contain orthologs of both of these genes; thus, the

  15. Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors.

    PubMed

    Young, Jo-Anne H; Logan, Brent R; Wu, Juan; Wingard, John R; Weisdorf, Daniel J; Mudrick, Cathryn; Knust, Kristin; Horowitz, Mary M; Confer, Dennis L; Dubberke, Erik R; Pergam, Steven A; Marty, Francisco M; Strasfeld, Lynne M; Brown, Janice Wes M; Langston, Amelia A; Schuster, Mindy G; Kaul, Daniel R; Martin, Stanley I; Anasetti, Claudio

    2016-02-01

    Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections

  16. Conductivity Probe

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Thermal and Electrical Conductivity Probe (TECP) for NASA's Phoenix Mars Lander took measurements in Martian soil and in the air.

    The needles on the end of the instrument were inserted into the Martian soil, allowing TECP to measure the propagation of both thermal and electrical energy. TECP also measured the humidity in the surrounding air.

    The needles on the probe are 15 millimeters (0.6 inch) long.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  17. MIP models and hybrid algorithms for simultaneous job splitting and scheduling on unrelated parallel machines.

    PubMed

    Eroglu, Duygu Yilmaz; Ozmutlu, H Cenk

    2014-01-01

    We developed mixed integer programming (MIP) models and hybrid genetic-local search algorithms for the scheduling problem of unrelated parallel machines with job sequence and machine-dependent setup times and with job splitting property. The first contribution of this paper is to introduce novel algorithms which make splitting and scheduling simultaneously with variable number of subjobs. We proposed simple chromosome structure which is constituted by random key numbers in hybrid genetic-local search algorithm (GAspLA). Random key numbers are used frequently in genetic algorithms, but it creates additional difficulty when hybrid factors in local search are implemented. We developed algorithms that satisfy the adaptation of results of local search into the genetic algorithms with minimum relocation operation of genes' random key numbers. This is the second contribution of the paper. The third contribution of this paper is three developed new MIP models which are making splitting and scheduling simultaneously. The fourth contribution of this paper is implementation of the GAspLAMIP. This implementation let us verify the optimality of GAspLA for the studied combinations. The proposed methods are tested on a set of problems taken from the literature and the results validate the effectiveness of the proposed algorithms. PMID:24977204

  18. Identification of novel Bruton's tyrosine kinase mutations in 10 unrelated subjects with X linked agammaglobulinaemia.

    PubMed Central

    Brooimans, R A; van den Berg, A J; Rijkers, G T; Sanders, L A; van Amstel, J K; Tilanus, M G; Grubben, M J; Zegers, B J

    1997-01-01

    Mutations of the Bruton's tyrosine kinase (Btk) gene cause X linked agammaglobulinaemia (XLA). This inherited immunodeficiency disease causes an arrest in B cell differentiation of pre-B cells to mature B cells. In this study we report the characterisation of mutations in the Btk gene in 10 unrelated XLA families. The screening approach we used was based on reverse transcriptase PCR and direct cycle sequencing of the amplified products followed by analysis of the observed mutations at the level of genomic DNA. The single strand confirmation polymorphism (SSCP) technique was used for assessment of the carriers in some of these families. Various mutations throughout the coding gene were observed, including missense and nonsense mutations, a deletion, and several splicing defects. None of the mutations except one has been previously described. There were three point mutations resulting in a single amino acid substitution. One of these missense mutations was observed in a conserved region of the PH domain, the other two were found in the src homology domain 2 that is involved in phosphotyrosyl peptide binding. Two mutations were single base pair substitutions resulting in premature stop codons. In four patients abnormal Btk transcripts were found that were the result of aberrant splicing. One small deletion was observed causing a frameshift and a secondary premature termination signal. Characterisation of the mutations responsible for XLA allowed us to diagnose the disease conclusively and identify the phenotypically normal female carriers. Images PMID:9192269

  19. Unrelated secondary reproductives in the neotropical termite Silvestritermes euamignathus (Isoptera: Termitidae).

    PubMed

    Haifig, Ives; Vargo, Edward L; Labadie, Paul; Costa-Leonardo, Ana Maria

    2016-02-01

    A termite colony is usually founded by a pair of alates, the primary reproductives, which produce all the nestmates. In some species, secondary reproductives appear to either replace the primaries or supplement colony reproduction. In termites, secondary reproductives are generally ergatoids derived from workers or nymphoids derived from nymphs. Silvestritermes euamignathus is a termite species that forms multiple nymphoid reproductives, and to date it was hypothesized that these secondary reproductives were the progeny of the primary founding reproductives. We developed markers for 12 microsatellite loci and used COI mitochondrial DNA (mtDNA) to genotype 59 nymphoid neotenics found in a colony of S. euamignathus to test this hypothesis. Our results showed that nymphoids of S. euamignathus are not all siblings. The microsatellite analysis suggests that the secondary reproductives derived from a minimum of four different pairs of reproductives belonging to at least two different matrilines. This is the first record of non-sibling secondary reproductives occupying the same nest in a higher termite. These unrelated reproductives might be the result of either pleometrotic colony foundation or colony fusion.

  20. A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated Viral Antagonists

    PubMed Central

    Esparo, Nicolle M.; Child, Stephanie J.; Geballe, Adam P.

    2016-01-01

    During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs) have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR) pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm) PKR (F489S) is sufficient to confer resistance to HCMVTRS1. Notably, this precise molecular determinant of PKR resistance has evolved under strong positive selection among primate PKR alleles and is positioned within the αG helix, which mediates the direct interaction of PKR with its substrate eIF2α. Remarkably, this same residue also impacts sensitivity to K3L, a poxvirus-encoded pseudosubstrate that structurally mimics eIF2α. Unlike K3L, TRS1 has no homology to eIF2α, suggesting that unrelated viral genes have convergently evolved to target this critical region of PKR. Despite its functional importance, the αG helix exhibits extraordinary plasticity, enabling adaptations that allow PKR to evade diverse viral antagonists while still maintaining its critical interaction with eIF2α. PMID:27780231

  1. Psychosocial effects of unrelated bone marrow donation: experiences of the National Marrow Donor Program.

    PubMed

    Butterworth, V A; Simmons, R G; Bartsch, G; Randall, B; Schimmel, M; Stroncek, D F

    1993-04-01

    In this study, we investigated the psychosocial effects of unrelated marrow donation. Survey questionnaires were administered pre-donation, shortly post-donation, and 1 year post-donation to all donors through the National Marrow Donor Program over a 3-year period. Univariate, bivariate, and multivariate analyses were then performed. Donors were generally quite positive about the donation 1 year post-donation: 87% felt it was "very worthwhile" and 91% would be willing to donate again in the future. Marrow donors were more likely than kidney donors to feel better about themselves as a result of the donation (P < .001). Donors with longer collection times, in general, had less positive psychosocial outcomes from the donation. Donors who experienced lower back pain or difficulty walking as a result of the donation were more likely to experience the donation as more stressful and painful than expected, but no more likely to experience it as less positive emotionally than donors who did not experience these side effects.

  2. Monoclonal antibodies against an identical short peptide sequence shared by two unrelated proteins.

    PubMed

    Schulze-Gahmen, U; Wilson, I A

    1989-01-01

    Antipeptide antibodies provide the opportunity to explore the molecular basis for antigen-antibody recognition and to test theories of immune recognition. We investigated the possibility of raising monoclonal antipeptide antibodies against a specific epitope consisting of six amino acid residues, which is common to two unrelated proteins. The goal of this investigation was to analyze the reactivity of these epitope specific antibodies towards the same sequence in these two different proteins. A correlation between antibody reactivity and secondary structures of the same peptide sequence in different proteins could help to understand the ability of antipeptide antibodies to react with their cognate sequence in intact folded proteins. Monoclonal antibodies were raised against one hexamer sequence, PGTAPK, that is present in both thioredoxin and Fab New lambda-light chain. The antipeptide antibodies reacted only with thioredoxin but not with Fab New in ELISA's, immune precipitation and Western blots. Determination of the antibody specificity through binding tests with peptide analogs revealed the influence of the residue N-terminal from the hexamer epitope on antibody binding. Because of the observed influence of the N-1 adjacent residue in peptide analogs, the discrimination between the protein antigens could not be interpreted clearly as the result of the different hexamer conformations present in the native structures of the two proteins. However, analysis of the antibody reactivity with peptide analogs with varying "frame residues" surrounding the hexamer epitope indicates the possible discrimination of different peptide conformations by the antibody.

  3. A polystyrene binding target-unrelated peptide isolated in the screening of phage display library.

    PubMed

    Bakhshinejad, Babak; Sadeghizadeh, Majid

    2016-11-01

    Phage display is a powerful methodology for the identification of peptide ligands binding to any desired target. However, the selection of target-unrelated peptides (TUPs) appears as a huge problem in the screening of phage display libraries through biopanning. The phage-displayed peptide TLHPAAD has been isolated both in our laboratory and by another reserach group on completely different screening targets prompting us to hypothesize that it may be a potential TUP. In the current study, we analyzed the binding characteristics and propagation rate of phage clone displaying TLHPAAD peptide (SW-TUP clone). The results of ELISA experiment and phage recovery assay provided strong support for the notion that SW-TUP phage binds to polystyrene with a significantly higher affinity than control phage clones. Furthermore, this polystyrene binding was demonstrated to occur in a concentration- and pH-dependent mode. Characterization of the propagation profile of phage clones within a specified time course revealed no statistically significant difference between the amplification rate of SW-TUP and control phages. Our findings lead us to the conclusion that SW-TUP phage clone with the displayed peptide TLHPAAD is not a true target binder and its selection in biopanning experiments results from its bidning affinity to the polystyrene surface of the solid phase.

  4. Unrelated secondary reproductives in the neotropical termite Silvestritermes euamignathus (Isoptera: Termitidae)

    NASA Astrophysics Data System (ADS)

    Haifig, Ives; Vargo, Edward L.; Labadie, Paul; Costa-Leonardo, Ana Maria

    2016-02-01

    A termite colony is usually founded by a pair of alates, the primary reproductives, which produce all the nestmates. In some species, secondary reproductives appear to either replace the primaries or supplement colony reproduction. In termites, secondary reproductives are generally ergatoids derived from workers or nymphoids derived from nymphs. Silvestritermes euamignathus is a termite species that forms multiple nymphoid reproductives, and to date it was hypothesized that these secondary reproductives were the progeny of the primary founding reproductives. We developed markers for 12 microsatellite loci and used COI mitochondrial DNA (mtDNA) to genotype 59 nymphoid neotenics found in a colony of S. euamignathus to test this hypothesis. Our results showed that nymphoids of S. euamignathus are not all siblings. The microsatellite analysis suggests that the secondary reproductives derived from a minimum of four different pairs of reproductives belonging to at least two different matrilines. This is the first record of non-sibling secondary reproductives occupying the same nest in a higher termite. These unrelated reproductives might be the result of either pleometrotic colony foundation or colony fusion.

  5. Phenological Adaptations in Ficus tikoua Exhibit Convergence with Unrelated Extra-Tropical Fig Trees

    PubMed Central

    Zhao, Ting-Ting; Compton, Stephen G.; Yang, Yong-Jiang; Wang, Rong; Chen, Yan

    2014-01-01

    Flowering phenology is central to the ecology and evolution of most flowering plants. In highly-specific nursery pollination systems, such as that involving fig trees (Ficus species) and fig wasps (Agaonidae), any mismatch in timing has serious consequences because the plants must balance seed production with maintenance of their pollinator populations. Most fig trees are found in tropical or subtropical habitats, but the dioecious Chinese Ficus tikoua has a more northerly distribution. We monitored how its fruiting phenology has adapted in response to a highly seasonal environment. Male trees (where fig wasps reproduce) had one to three crops annually, whereas many seed-producing female trees produced only one fig crop. The timing of release of Ceratosolen fig wasps from male figs in late May and June was synchronized with the presence of receptive figs on female trees, at a time when there were few receptive figs on male trees, thereby ensuring seed set while allowing remnant pollinator populations to persist. F. tikoua phenology has converged with those of other (unrelated) northern Ficus species, but there are differences. Unlike F. carica in Europe, all F. tikoua male figs contain male flowers, and unlike F. pumila in China, but like F. carica, it is the second annual generation of adult wasps that pollinate female figs. The phenologies of all three temperate fig trees generate annual bottlenecks in the size of pollinator populations and for female F. tikoua also a shortage of fig wasps that results in many figs failing to be pollinated. PMID:25474008

  6. False Memory ≠ False Memory: DRM Errors Are Unrelated to the Misinformation Effect

    PubMed Central

    Ost, James; Blank, Hartmut; Davies, Joanna; Jones, Georgina; Lambert, Katie; Salmon, Kelly

    2013-01-01

    The DRM method has proved to be a popular and powerful, if controversial, way to study ‘false memories’. One reason for the controversy is that the extent to which the DRM effect generalises to other kinds of memory error has been neither satisfactorily established nor subject to much empirical attention. In the present paper we contribute data to this ongoing debate. One hundred and twenty participants took part in a standard misinformation effect experiment, in which they watched some CCTV footage, were exposed to misleading post-event information about events depicted in the footage, and then completed free recall and recognition tests. Participants also completed a DRM test as an ostensibly unrelated filler task. Despite obtaining robust misinformation and DRM effects, there were no correlations between a broad range of misinformation and DRM effect measures (mean r  = −.01). This was not due to reliability issues with our measures or a lack of power. Thus DRM ‘false memories’ and misinformation effect ‘false memories’ do not appear to be equivalent. PMID:23573186

  7. AC Resonant charger with charge rate unrelated to primary power frequency

    DOEpatents

    Watson, Harold

    1982-01-01

    An AC resonant charger for a capacitive load, such as a PFN, is provided with a variable repetition rate unrelated to the frequency of a multi-phase AC power source by using a control unit to select and couple the phase of the power source to the resonant charger in order to charge the capacitive load with a phase that is the next to begin a half cycle. For optimum range in repetition rate and increased charging voltage, the resonant charger includes a step-up transformer and full-wave rectifier. The next phase selected may then be of either polarity, but is always selected to be of a polarity opposite the polarity of the last phase selected so that the transformer core does not saturate. Thyristors are used to select and couple the correct phase just after its zero crossover in response to a sharp pulse generated by a zero-crossover detector. The thyristor that is turned on then automatically turns off after a full half cycle of its associated phase input. A full-wave rectifier couples the secondary winding of the transformer to the load so that the load capacitance is always charged with the same polarity.

  8. Ac resonant charger with charge rate unrelated to preimary power requency

    DOEpatents

    Not Available

    1979-12-07

    An ac resonant charger for a capacitive load, such as a pulse forming network (PFN), is provided with a variable repetition rate unrelated to the frequency of a multi-phase ac power source by using a control unit to select and couple the phase of the power source to the resonant charger in order to charge the capacitive load with a phase that is the next to begin a half cycle. For optimum range in repetition rate and increased charging voltage, the resonant charger includes a step-up transformer and full-wave rectifier. The next phase selected may then be of either polarity, but is always selected to be of a polarity opposite the polarity of the last phase selected so that the transformer core does not saturate. Thyristors are used to select and couple the correct phase just after its zero crossover in response to a sharp pulse generated by a zero-crossover detector. The thyristor that is turned on then automatically turns off after a full half cycle of its associated phase input. A full-wave rectifier couples the secondary winding of the transformer to the load so that the load capacitance is always charged with the same polarity.

  9. Unique genomic structure and distinct mitotic behavior of ring chromosome 21 in two unrelated cases.

    PubMed

    Zhang, H Z; Xu, F; Seashore, M; Li, P

    2012-01-01

    A ring chromosome replacing a normal chromosome could involve variable structural rearrangements and mitotic instability. However, most previously reported cases lacked further genomic characterization. High-resolution oligonucleotide array comparative genomic hybridization with single-nucleotide polymorphism typing (aCGH+SNP) was used to study 2 unrelated cases with a ring chromosome 21. Case 1 had severe myopia, hypotonia, joint hypermobility, speech delay, and dysmorphic features. aCGH detected a 1.275-Mb duplication of 21q22.12-q22.13 and a 6.731-Mb distal deletion at 21q22.2. Case 2 showed severe growth and developmental retardations, intractable seizures, and dysmorphic features. aCGH revealed a contiguous pattern of a 3.612- Mb deletion of 21q22.12-q22.2, a 4.568-Mb duplication of 21q22.2-q22.3, and a 2.243-Mb distal deletion at 21q22.3. Mitotic instability was noted in 13, 30, and 76% of in vitro cultured metaphase cells, interphase cells, and leukocyte DNA, respectively. The different phenotypes of these 2 cases are likely associated with the unique genomic structure and distinct mitotic behavior of their ring chromosome 21. These 2 cases represent a subtype of ring chromosome 21 probably involving somatic dicentric ring breakage and reunion. A cytogenomic approach is proposed for characterizing the genomic structure and mitotic instability of ring chromosome abnormalities.

  10. Motivation, intentionality, and mind wandering: Implications for assessments of task-unrelated thought.

    PubMed

    Seli, Paul; Cheyne, James Allan; Xu, Mengran; Purdon, Christine; Smilek, Daniel

    2015-09-01

    Researchers of mind wandering frequently assume that (a) participants are motivated to do well on the tasks they are given, and (b) task-unrelated thoughts (TUTs) that occur during task performance reflect unintentional, unwanted thoughts that occur despite participants' best intentions to maintain task-focus. Given the relatively boring and tedious nature of most mind-wandering tasks, however, there is the possibility that some participants have little motivation to do well on such tasks, and that this lack of motivation might in turn result in increases specifically in intentional TUTs. In the present study, we explored these possibilities, finding that individuals reporting lower motivation to perform well on a sustained-attention task reported more intentional relative to unintentional TUTs compared with individuals reporting higher motivation. Interestingly, our results indicate that the extent to which participants engage in intentional versus unintentional TUTs does not differentially relate to performance: both types of off-task thought were found to be equally associated with performance decrements. Participants with low levels of task-motivation also engaged in more overall TUTs, however, and this increase in TUTs was associated with greater performance decrements. We discuss these findings in the context of the literature on mind wandering, highlighting the importance of assessing the intentionality of TUTs and motivation to perform well on tasks assessing mind wandering.

  11. Unrelated secondary reproductives in the neotropical termite Silvestritermes euamignathus (Isoptera: Termitidae).

    PubMed

    Haifig, Ives; Vargo, Edward L; Labadie, Paul; Costa-Leonardo, Ana Maria

    2016-02-01

    A termite colony is usually founded by a pair of alates, the primary reproductives, which produce all the nestmates. In some species, secondary reproductives appear to either replace the primaries or supplement colony reproduction. In termites, secondary reproductives are generally ergatoids derived from workers or nymphoids derived from nymphs. Silvestritermes euamignathus is a termite species that forms multiple nymphoid reproductives, and to date it was hypothesized that these secondary reproductives were the progeny of the primary founding reproductives. We developed markers for 12 microsatellite loci and used COI mitochondrial DNA (mtDNA) to genotype 59 nymphoid neotenics found in a colony of S. euamignathus to test this hypothesis. Our results showed that nymphoids of S. euamignathus are not all siblings. The microsatellite analysis suggests that the secondary reproductives derived from a minimum of four different pairs of reproductives belonging to at least two different matrilines. This is the first record of non-sibling secondary reproductives occupying the same nest in a higher termite. These unrelated reproductives might be the result of either pleometrotic colony foundation or colony fusion. PMID:26781111

  12. Acute Uterine Bleeding Unrelated to Pregnancy: A Southern California Permanente Medical Group Practice Guideline

    PubMed Central

    Munro, Malcolm G

    2013-01-01

    Acute uterine bleeding unrelated to pregnancy has been defined as bleeding “sufficient in volume as to, in the opinion of the treating clinician, require urgent or emergent intervention.” The Southern California Permanente Medical Group updated its guidelines for the management of this condition on the basis of the best available evidence, as identified in a systematic review of the available literature. Given the paucity of studies evaluating this condition, the guidelines, by necessity, include recommendations largely based on opinion or other sources such as case series that are, in general, categorized as low-quality evidence. Medical interventions with single or combined gonadal steroidal agents administered parenterally or orally show promise, but more high-quality studies are needed to better define the appropriate drugs, dose, and administrative scheduling. There is also some evidence that intrauterine tamponade may be useful in at least selected cases. Special attention must be paid to both diagnosing and treating inherited disorders of hemostasis, such as von Willebrand disease, that may otherwise be underdiagnosed in both adolescent and adult women. PMID:24355890

  13. Corruption of phage display libraries by target-unrelated clones: diagnosis and countermeasures.

    PubMed

    Thomas, William D; Golomb, Miriam; Smith, George P

    2010-12-15

    Phage display is used to discover peptides or proteins with a desired target property-most often, affinity for a target selector molecule. Libraries of phage clones displaying diverse surface peptides are subject to a selection process designed to enrich for the target behavior and subsequently propagated to restore phage numbers. A recurrent problem is enrichment of clones, called target-unrelated phages or peptides (TUPs), that lack the target behavior. Many TUPs are propagation related; they have mutations conferring a growth advantage and are enriched during the propagations accompanying selection. Unlike other filamentous phage libraries, fd-tet-based libraries are relatively resistant to propagation-related TUP corruption. Their minus-strand origin is disrupted by a large cassette that simultaneously confers resistance to tetracycline and imposes a rate-limiting growth defect that cannot be bypassed with simple mutations. Nonetheless, a new type of propagation-related TUP emerged in the output of in vivo selections from an fd-tet library. The founding clone had a complex rearrangement that restored the minus-strand origin while retaining tetracycline resistance. The rearrangement involved two recombination events, one with a contaminant having a wild-type minus-strand origin. The founder's infectivity advantage spread by simple recombination to clones displaying different peptides. We propose measures for minimizing TUP corruption.

  14. Functional Analysis of A Novel Splicing Mutation in The Mutase Gene of Two Unrelated Pedigrees

    PubMed Central

    Miryounesi, Mohammad; Pasalar, Parvin; Keramatipour, Mohammad

    2016-01-01

    Objective Methylmalonic acidura (MMA) is a rare autosomal recessive inborn error of metabolism. In this study we present a novel nucleotide change in the mutase (MUT) gene of two unrelated Iranian pedigrees and introduce the methods used for its functional analysis. Materials and Methods Two probands with definite diagnosis of MMA and a common novel variant in the MUT were included in a descriptive study. Bioinformatic prediction of the splicing variant was done with different prediction servers. Reverse transcriptionpolymerase chain reaction (RT-PCR) was done for splicing analysis and the products were analyzed by sequencing. Results The included index patients showed elevated levels of propionylcarnitine (C3). Urine organic acid analysis confirmed the diagnosis of MMA, and screening for mutations in the MUT revealed a novel C to G variation at the 3´ splice acceptor site in intron 12. In silico analysis suggested the change as a mutation in a conserved sequence. The splicing analysis showed that the C to G nucleotide change at position -3 in the acceptor splice site can lead to retention of the intron 12 sequence. Conclusion This is the first report of a mutation at the position -3 in the MUT intron 12 (c.2125-3C>G). The results suggest that the identified variation can be associated with the typical clinical manifestations of MMA. PMID:27602322

  15. Trends in unrelated-donor kidney transplantation in the developing world.

    PubMed

    Barsoum, Rashad S

    2008-11-01

    Living unrelated donors (LUDs) constitute an incremental source of kidneys for transplantation at a global level. Excellent outcomes are reported, superior to those of deceased-donor transplantation and comparable to related donor transplantation. LUD include six categories: spouses, distant relatives, paired-exchange, living-deceased exchange, and non-directed and directed donors. Although a financial reward may be involved in any of these categories, it is in the declared selling of organs that ethical concerns have intensified. There are three patterns of paid LUDs in the developing world: organized, erratic and commercial. The only model of organized LUDs is in Iran, where a central agency assigns and compensates the donors. Erratic LUD transplantation has been experienced, and subsequently banned, in the development of transplant programmes in most developing countries. However, the tightness and enforcement of the official ban are geographically different, providing variable room for uncontrolled trafficking. Commercial transplantation has, thus, become phenomenal in a few countries, gradually evolving into an organized business that follows market dynamics, including advertisement, brokerage, commissions, auctions and tourism. While most international organizations and activist groups condemn commercial transplantation, it is often perceived, in certain cultures and under particular socioeconomic standards, as a human right that meets the demands of all stakeholders, and should be organized rather than declined just for the purpose of meeting the values of a third party.

  16. Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs

    PubMed Central

    Tribouillard-Tanvier, Déborah; Dos Reis, Suzana; Gug, Fabienne; Voisset, Cécile; Béringue, Vincent; Sabate, Raimon; Kikovska, Ema; Talarek, Nicolas; Bach, Stéphane; Huang, Chenhui; Desban, Nathalie; Saupe, Sven J.; Supattapone, Surachai; Thuret, Jean-Yves; Chédin, Stéphane; Vilette, Didier; Galons, Hervé; Sanyal, Suparna; Blondel, Marc

    2008-01-01

    Background 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases. Methodology/Principal Findings Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome. Conclusion/Significance 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity. PMID:18478094

  17. MIP Models and Hybrid Algorithms for Simultaneous Job Splitting and Scheduling on Unrelated Parallel Machines

    PubMed Central

    Ozmutlu, H. Cenk

    2014-01-01

    We developed mixed integer programming (MIP) models and hybrid genetic-local search algorithms for the scheduling problem of unrelated parallel machines with job sequence and machine-dependent setup times and with job splitting property. The first contribution of this paper is to introduce novel algorithms which make splitting and scheduling simultaneously with variable number of subjobs. We proposed simple chromosome structure which is constituted by random key numbers in hybrid genetic-local search algorithm (GAspLA). Random key numbers are used frequently in genetic algorithms, but it creates additional difficulty when hybrid factors in local search are implemented. We developed algorithms that satisfy the adaptation of results of local search into the genetic algorithms with minimum relocation operation of genes' random key numbers. This is the second contribution of the paper. The third contribution of this paper is three developed new MIP models which are making splitting and scheduling simultaneously. The fourth contribution of this paper is implementation of the GAspLAMIP. This implementation let us verify the optimality of GAspLA for the studied combinations. The proposed methods are tested on a set of problems taken from the literature and the results validate the effectiveness of the proposed algorithms. PMID:24977204

  18. Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients.

    PubMed

    Juanes, Matías; Di Palma, Isabel; Ciaccio, Marta; Marino, Roxana; Ramírez, Pablo C; Pérez Garrid, Natalia; Maceiras, Mercedes; Lazzati, Juan M; Rivarola, Marco A; Belgorosky, Alicia

    2016-01-01

    Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives. In silico tools were applied to identify the functional impact of newly found variants (Polyphen2, SIFT, Mutation Taster). We identified two novel heterozygous missense variations in two unrelated patients, p.Arg231Gln and p.Arg226Leu, located in the repressor domain of the protein. Both variations affect highly conserved amino acids of the Gli2 protein and were not found in the available databases. In silico tools suggest that these variations might be disease causing. Our study suggests that the GLI2 gene may be one of the candidate genes to analyze when an association of pituitary hormone deficiency and developmental defects in posterior pituitary gland. The highly variable phenotype found suggests the presence of additional unknown factors that could contribute to the phenotype observed in these patients. PMID:27576279

  19. MIP models and hybrid algorithms for simultaneous job splitting and scheduling on unrelated parallel machines.

    PubMed

    Eroglu, Duygu Yilmaz; Ozmutlu, H Cenk

    2014-01-01

    We developed mixed integer programming (MIP) models and hybrid genetic-local search algorithms for the scheduling problem of unrelated parallel machines with job sequence and machine-dependent setup times and with job splitting property. The first contribution of this paper is to introduce novel algorithms which make splitting and scheduling simultaneously with variable number of subjobs. We proposed simple chromosome structure which is constituted by random key numbers in hybrid genetic-local search algorithm (GAspLA). Random key numbers are used frequently in genetic algorithms, but it creates additional difficulty when hybrid factors in local search are implemented. We developed algorithms that satisfy the adaptation of results of local search into the genetic algorithms with minimum relocation operation of genes' random key numbers. This is the second contribution of the paper. The third contribution of this paper is three developed new MIP models which are making splitting and scheduling simultaneously. The fourth contribution of this paper is implementation of the GAspLAMIP. This implementation let us verify the optimality of GAspLA for the studied combinations. The proposed methods are tested on a set of problems taken from the literature and the results validate the effectiveness of the proposed algorithms.

  20. A polystyrene binding target-unrelated peptide isolated in the screening of phage display library.

    PubMed

    Bakhshinejad, Babak; Sadeghizadeh, Majid

    2016-11-01

    Phage display is a powerful methodology for the identification of peptide ligands binding to any desired target. However, the selection of target-unrelated peptides (TUPs) appears as a huge problem in the screening of phage display libraries through biopanning. The phage-displayed peptide TLHPAAD has been isolated both in our laboratory and by another reserach group on completely different screening targets prompting us to hypothesize that it may be a potential TUP. In the current study, we analyzed the binding characteristics and propagation rate of phage clone displaying TLHPAAD peptide (SW-TUP clone). The results of ELISA experiment and phage recovery assay provided strong support for the notion that SW-TUP phage binds to polystyrene with a significantly higher affinity than control phage clones. Furthermore, this polystyrene binding was demonstrated to occur in a concentration- and pH-dependent mode. Characterization of the propagation profile of phage clones within a specified time course revealed no statistically significant difference between the amplification rate of SW-TUP and control phages. Our findings lead us to the conclusion that SW-TUP phage clone with the displayed peptide TLHPAAD is not a true target binder and its selection in biopanning experiments results from its bidning affinity to the polystyrene surface of the solid phase. PMID:27555439

  1. Phenological adaptations in Ficus tikoua exhibit convergence with unrelated extra-tropical fig trees.

    PubMed

    Zhao, Ting-Ting; Compton, Stephen G; Yang, Yong-Jiang; Wang, Rong; Chen, Yan

    2014-01-01

    Flowering phenology is central to the ecology and evolution of most flowering plants. In highly-specific nursery pollination systems, such as that involving fig trees (Ficus species) and fig wasps (Agaonidae), any mismatch in timing has serious consequences because the plants must balance seed production with maintenance of their pollinator populations. Most fig trees are found in tropical or subtropical habitats, but the dioecious Chinese Ficus tikoua has a more northerly distribution. We monitored how its fruiting phenology has adapted in response to a highly seasonal environment. Male trees (where fig wasps reproduce) had one to three crops annually, whereas many seed-producing female trees produced only one fig crop. The timing of release of Ceratosolen fig wasps from male figs in late May and June was synchronized with the presence of receptive figs on female trees, at a time when there were few receptive figs on male trees, thereby ensuring seed set while allowing remnant pollinator populations to persist. F. tikoua phenology has converged with those of other (unrelated) northern Ficus species, but there are differences. Unlike F. carica in Europe, all F. tikoua male figs contain male flowers, and unlike F. pumila in China, but like F. carica, it is the second annual generation of adult wasps that pollinate female figs. The phenologies of all three temperate fig trees generate annual bottlenecks in the size of pollinator populations and for female F. tikoua also a shortage of fig wasps that results in many figs failing to be pollinated.

  2. Related hematopoietic cell donor care: is there a role for unrelated donor registries?

    PubMed

    Anthias, C; van Walraven, S M; Sørensen, B S; de Faveri, G N; Fechter, M; Cornish, J; Bacigalupo, A; Müller, C; Boo, M; Shaw, B E

    2015-05-01

    In almost half of allogeneic hematopoietic progenitor cell (HPC) transplants, a related donor (RD) is used, yet a lack of standardized guidelines means that their care is heterogeneous. Changes to regulatory standards aim to improve uniformity, but adherence to these regulations can prove logistically difficult for the transplant centers (TCs) managing RDs. Discussion has ensued around possible alternative models of related donor care and a session at the European Society for Blood and Marrow Transplantation (EBMT) annual meeting in 2013 debated the question of whether a role exists for unrelated donor registries in the management of 'related' donors. In this overview, we discuss the issues raised at this debate and the pros and cons of donor registry involvement in various aspects of RD management. By examining existing models of related donor care that have been adopted by members of the World Marrow Donor Association (WMDA), we look for ways to enhance and homogenize RD care, while also enabling transplant centers to meet standards required for mandatory accreditation.

  3. [Transplantation of bone marrow from unrelated donors in Italy: activity and results].

    PubMed

    Dini, G; Miano, M; Morreale, G; Lanino, E

    1999-01-01

    Unrelated donor (UD) bone marrow transplantation (BMT) represents an attractive option for patients with haematological, oncological or genetic diseases lacking a compatible familiar donor. Between September 1988 and December 1997 the search of a donor has been activated for 1724 patients in Italy. Until May 1998, 413 BMT from UD have been performed in 28 different authorized italian centres. Forty out of these patients were affected by genetic diseases apart from SCID (severe combined immunodeficiency). Sixty-month disease free survival (DFS) of this group was 62%. Seventy-four out of 215 children with acute lymphoblastic leukemia (ALL) for whom a donor search was started underwent a BMT. Six year DFS was 25%. Fifty-nine out of 379 patients with chronic myeloid leukemia (CML) for whom a donor search was activated underwent BMT. Forty-eight month DFS was 41.5%. Inborn errors curable with BMT, relapsed ALL and CML represent an absolute indication for UD BMT. In these cases donor search should be activated yearly.

  4. Functional Analysis of A Novel Splicing Mutation in The Mutase Gene of Two Unrelated Pedigrees

    PubMed Central

    Miryounesi, Mohammad; Pasalar, Parvin; Keramatipour, Mohammad

    2016-01-01

    Objective Methylmalonic acidura (MMA) is a rare autosomal recessive inborn error of metabolism. In this study we present a novel nucleotide change in the mutase (MUT) gene of two unrelated Iranian pedigrees and introduce the methods used for its functional analysis. Materials and Methods Two probands with definite diagnosis of MMA and a common novel variant in the MUT were included in a descriptive study. Bioinformatic prediction of the splicing variant was done with different prediction servers. Reverse transcriptionpolymerase chain reaction (RT-PCR) was done for splicing analysis and the products were analyzed by sequencing. Results The included index patients showed elevated levels of propionylcarnitine (C3). Urine organic acid analysis confirmed the diagnosis of MMA, and screening for mutations in the MUT revealed a novel C to G variation at the 3´ splice acceptor site in intron 12. In silico analysis suggested the change as a mutation in a conserved sequence. The splicing analysis showed that the C to G nucleotide change at position -3 in the acceptor splice site can lead to retention of the intron 12 sequence. Conclusion This is the first report of a mutation at the position -3 in the MUT intron 12 (c.2125-3C>G). The results suggest that the identified variation can be associated with the typical clinical manifestations of MMA.

  5. Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide, Surugamide F.

    PubMed

    Ninomiya, Akihiro; Katsuyama, Yohei; Kuranaga, Takefumi; Miyazaki, Masayuki; Nogi, Yuichi; Okada, Shigeru; Wakimoto, Toshiyuki; Ohnishi, Yasuo; Matsunaga, Shigeki; Takada, Kentaro

    2016-09-15

    Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamides A-E (inhibitors of cathepsin B), we found a putative gene cluster consisting of four successive non-ribosomal peptide synthetase (NRPS) genes, surA, surB, surC, and surD. Prediction of amino acid sequence based on the NRPSs and gene inactivation revealed that surugamides A-E are produced by two NRPS genes, surA and surD, which were separated by two NRPS genes, surB and surC. The latter genes are responsible for the biosynthesis of an unrelated peptide, surugamide F. The pattern of intercalation observed in the sur genes is unprecedented. The structure of surugamide F, a linear decapeptide containing one 3-amino-2-methylpropionic acid (AMPA) residue, was determined by spectroscopic methods and was confirmed by solid-phase peptide synthesis. PMID:27443244

  6. Transcriptional profiles for glutamate transporters reveal differences between organophosphates but similarities with unrelated neurotoxicants.

    PubMed

    Slotkin, Theodore A; Lobner, Doug; Seidler, Frederic J

    2010-08-30

    The developmental neurotoxicity of organophosphates involves mechanisms other than their shared property as cholinesterase inhibitors, among which are excitotoxicity and oxidative stress. We used PC12 cells as a neurodevelopmental model to compare the effects of chlorpyrifos and diazinon on the expression of genes encoding glutamate transporters. Chlorpyrifos had a greater effect in cells undergoing nerve growth factor-induced neurodifferentiation as compared to undifferentiated PC12 cells, with peak sensitivity at the initiation of differentiation, reflecting a global upregulation of all the glutamate transporter genes expressed in this cell line. In differentiating cells, chlorpyrifos had a significantly greater effect than did diazinon and concordance analysis indicated no resemblance in their expression patterns. At the same time, the smaller effects of diazinon were highly concordant with those of an organochlorine pesticide (dieldrin) and a metal (divalent nickel). We also performed similar evaluations for the cystine/glutamate exchanger, which provides protection against oxidative stress by moving cystine into the cell; again, chlorpyrifos had the greatest effect, in this case reducing expression in undifferentiated and differentiating cells. Our results point to excitotoxicity and oxidative stress as major contributors to the noncholinesterase mechanisms that distinguish the neurodevelopmental outcomes between different organophosphates while providing a means whereby apparently unrelated neurotoxicants may produce similar outcomes. PMID:20600679

  7. Molecular cytogenetic and phenotypic characterization of ring chromosome 13 in three unrelated patients.

    PubMed

    Abdallah-Bouhjar, Inesse B; Mougou-Zerelli, Soumaya; Hannachi, Hanene; Gmidène, Abir; Labalme, Audrey; Soyah, Najla; Sanlaville, Damien; Saad, Ali; Elghezal, Hatem

    2013-09-01

    We report on the cytogenetic and molecular investigations of constitutional de-novo ring chromosome 13s in three unrelated patients for better understanding and delineation of the phenotypic variability characterizing this genomic rearrangement. The patient's karyotypes were as follows: 46,XY,r(13)(p11q34) dn for patients 1 and 2 and 46,XY,r(13)(p11q14) dn for patient 3, as a result of the deletion in the telomeric regions of chromosome 13. The patients were, therefore, monosomic for the segment 13q34 → 13qter; in addition, for patient 3, the deletion was larger, encompassing the segment 13q14 → 13qter. Fluorescence in situ hybridization confirmed these rearrangement and array CGH technique showed the loss of at least 2.9 Mb on the short arm and 4.7 Mb on the long arm of the chromosome 13 in patient 2. Ring chromosome 13 (r(13)) is associated with several phenotypic features like intellectual disability, marked short stature, brain and heart defects, microcephaly and genital malformations in males, including undescended testes and hypospadias. However, the hearing loss and speech delay that were found in our three patients have rarely been reported with ring chromosome 13. Although little is known about its etiology, there is interesting evidence for a genetic cause for the ring chromosome 13. We thus performed a genotype-phenotype correlation analysis to ascertain the contribution of ring chromosome 13 to the clinical features of our three cases. PMID:27625853

  8. The effect of obesity on outcome of unrelated cord blood transplant in children with malignant diseases.

    PubMed

    Pine, M; Wang, L; Harrell, F E; Calder, C; Manes, B; Evans, M; Domm, J; Frangoul, H

    2011-10-01

    Obesity has become a pandemic, affecting both children and adults. We sought to determine the effect of obesity among 200 children who were prospectively enrolled on a multicenter cord blood transplant (CBT) trial. All patients received myeloablative preparative regimens. Children were classified into groups according to body mass index percentile. Normal weight was defined as body mass index between the 5th and 85th percentile (n=117), overweight between the 85th and 95th percentile (n=35) and obesity above 95th percentile (n=39) for age and gender. A total of 55 patients (27%) had AML, 113 patients (57%) had ALL and 32 patients (16%) had other malignant diseases. There was no evidence for a difference in all major characteristics among the groups. Time to neutrophil and platelet engraftment, TRM, risk of acute GVHD, disease-free survival and OS were not significantly different in overweight or obese patients compared with normal weight patients. There was a trend towards increased risk of chronic GVHD in obese patients (P=0.05) compared with normal weight patients. In conclusion, there is insufficient evidence from this sample that obesity has an effect on multiple outcomes after unrelated CBT in children with malignant diseases.

  9. Three's company: two or more unrelated receptors pair with the same ligand.

    PubMed

    Ben-Shlomo, Izhar; Hsueh, Aaron J W

    2005-05-01

    Intercellular communication relies on signal transduction mediated by extracellular ligands and their receptors. Although the ligand-receptor interaction is usually a two-player event, there are selective examples of one polypeptide ligand interacting with more than one phylogenetically unrelated receptor. Likewise, a few receptors interact with more than one polypeptide ligand, and sometimes with more than one coreceptor, likely through an interlocking of unique protein domains. Phylogenetic analyses suggest that for certain triumvirates, the matching events could have taken place at different evolutionary times. In contrast to a few polypeptide ligands interacting with more than one receptor, we found that many small nonpeptide ligands have been paired with two or more plasma membrane receptors, nuclear receptors, or channels. The observation that many small ligands are paired with more than one receptor type highlights the utilitarian use of a limited number of cellular components during metazoan evolution. These conserved ligands are ubiquitous cell metabolites likely favored by natural selection to establish novel regulatory networks. They likely possess structural features useful for designing agonistic and antagonistic drugs to target diverse receptors.

  10. Same-Age Unrelated Siblings: A Unique Test of Within-Family Environmental Influences on IQ Similarity.

    ERIC Educational Resources Information Center

    Segal, Nancy L.

    1997-01-01

    Pairs of genetically unrelated children reared as same-age siblings offer a design for investigating genetic and environmental influences on behavior. Results with 21 pairs support an explanatory model of intelligence that includes genetic factors. Shared environment appeared to have a very small effect on intellectual development. (SLD)

  11. Cytogenetic analysis of multifocal breast carcinomas: detection of karyotypically unrelated clones as well as clonal similarities between tumour foci.

    PubMed Central

    Teixeira, M. R.; Pandis, N.; Bardi, G.; Andersen, J. A.; Mandahl, N.; Mitelman, F.; Heim, S.

    1994-01-01

    Cytogenetic analysis was performed on short-term cell cultures of two foci (A and B) from each of three multifocal breast carcinomas. In case I, four clones (three related and one unrelated) were detected in sample A. In sample B, two of the three related clones and the unrelated clone seen in A were found, as was also a third subclone showing a pattern of clonal evolution slightly different from that detected in A. In cases II and III, multiple cytogenetically unrelated clones were found in A and B, with only one clone being shared by both foci in each case. Our finding of cytogenetic similarities between macroscopically distinct tumour lesions indicates that the multifocality reflects intramammary tumour spread rather than the synchronous emergence of pathogenetically independent carcinomas within the same breast. On the other hand, the detection of karyotypic heterogeneity in the form of cytogenetically unrelated clones in all foci suggests that human breast carcinoma may be polyclonal. This polyclonality may be part of the explanation for the cellular heterogeneity commonly seen at the phenotypic level in breast cancer. Images Figure 2 Figure 3 PMID:7947098

  12. Brief Report: Peculiar Evolution of Autistic Behaviors in Two Unrelated Children with Brachidactyly-Mental Retardation Syndrome

    ERIC Educational Resources Information Center

    Mazzone, Luigi; Vassena, Lia; Ruta, Liliana; Mugno, Diego; Galesi, Ornella; Fichera, Marco

    2012-01-01

    Brachidactyly-Mental Retardation (BDMR) Syndrome (MIM 600430) is associated with terminal deletions at chromosome 2q37 and a limited number of studies also reported an association between 2q37 [right arrow] qter deletion and autism. Herein we describe two cases of autism in unrelated children with BDMR Syndrome, showing physical, cognitive,…

  13. New Developments in Tax Exempt Institutions. Exempt Organizations Which Lend Securities Risk Imposition of Unrelated Business Tax

    ERIC Educational Resources Information Center

    Stern, Sue S.; Sullivan, Richard B.

    1976-01-01

    The practice by exempt organizations of lending securities to brokerage houses is becoming more common. The possibility is weighed that organizations may encounter unrelated business tax assessments if the practice is classified as a trade or business. The authors examine the concept of trade or business in other tax settings and explore the…

  14. 36 CFR 1275.52 - Restriction of materials of general historical significance unrelated to abuses of governmental...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Restriction of materials of general historical significance unrelated to abuses of governmental power. 1275.52 Section 1275.52 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION NIXON PRESIDENTIAL...

  15. 36 CFR 1275.52 - Restriction of materials of general historical significance unrelated to abuses of governmental...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Restriction of materials of general historical significance unrelated to abuses of governmental power. 1275.52 Section 1275.52 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION NIXON PRESIDENTIAL...

  16. 36 CFR 1275.52 - Restriction of materials of general historical significance unrelated to abuses of governmental...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Restriction of materials of general historical significance unrelated to abuses of governmental power. 1275.52 Section 1275.52 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION NIXON PRESIDENTIAL...

  17. 36 CFR 1275.52 - Restriction of materials of general historical significance unrelated to abuses of governmental...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Restriction of materials of general historical significance unrelated to abuses of governmental power. 1275.52 Section 1275.52 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION NIXON PRESIDENTIAL...

  18. 36 CFR 1275.52 - Restriction of materials of general historical significance unrelated to abuses of governmental...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Restriction of materials of general historical significance unrelated to abuses of governmental power. 1275.52 Section 1275.52 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION NIXON PRESIDENTIAL...

  19. 26 CFR 1.512(a)-5T - Questions and answers relating to the unrelated business taxable income of organizations...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... apply to existing reserves for post-retirement medical or life insurance benefits? A-4: (a) Section 512... reserves for post-retirement medical or life insurance benefits will not be treated as unrelated business taxable income. An existing reserve for post-retirement medical or life insurance benefits (as defined...

  20. Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

    PubMed

    Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K

    2015-10-01

    Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability.

  1. Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women

    PubMed Central

    Reinl, Erin L.; Cabeza, Rafael; Gregory, Ismail A.; Cahill, Alison G.; England, Sarah K.

    2015-01-01

    Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca2+ influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd3+-sensitive, Na+-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na+-dependent leak current in human myometrium and demonstrate that the Na+-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca2+ and K+ channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd3+ or by superfusing the cells with a Na+-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd3+-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. PMID:26134120

  2. Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

    PubMed Central

    Franchini, Lucía F.; López-Leal, Rodrigo; Nasif, Sofía; Beati, Paula; Gelman, Diego M.; Low, Malcolm J.; de Souza, Flávio J. S.; Rubinstein, Marcelo

    2011-01-01

    The proopiomelanocortin gene (POMC) is expressed in a group of neurons present in the arcuate nucleus of the hypothalamus. Neuron-specific POMC expression in mammals is conveyed by two distal enhancers, named nPE1 and nPE2. Previous transgenic mouse studies showed that nPE1 and nPE2 independently drive reporter gene expression to POMC neurons. Here, we investigated the evolutionary mechanisms that shaped not one but two neuron-specific POMC enhancers and tested whether nPE1 and nPE2 drive identical or complementary spatiotemporal expression patterns. Sequence comparison among representative genomes of most vertebrate classes and mammalian orders showed that nPE1 is a placental novelty. Using in silico paleogenomics we found that nPE1 originated from the exaptation of a mammalian-apparent LTR retrotransposon sometime between the metatherian/eutherian split (147 Mya) and the placental mammal radiation (≈90 Mya). Thus, the evolutionary origin of nPE1 differs, in kind and time, from that previously demonstrated for nPE2, which was exapted from a CORE-short interspersed nucleotide element (SINE) retroposon before the origin of prototherians, 166 Mya. Transgenic mice expressing the fluorescent markers tomato and EGFP driven by nPE1 or nPE2, respectively, demonstrated coexpression of both reporter genes along the entire arcuate nucleus. The onset of reporter gene expression guided by nPE1 and nPE2 was also identical and coincidental with the onset of Pomc expression in the presumptive mouse diencephalon. Thus, the independent exaptation of two unrelated retroposons into functional analogs regulating neuronal POMC expression constitutes an authentic example of convergent molecular evolution of cell-specific enhancers. PMID:21876128

  3. Additive interactions of unrelated viruses in mixed infections of cowpea (Vigna unguiculata L. Walp).

    PubMed

    Nsa, Imade Y; Kareem, Kehinde T

    2015-01-01

    This study was carried out to determine the effects of single infections and co-infections of three unrelated viruses on three cowpea cultivars (one commercial cowpea cultivar "White" and 2 IITA lines; IT81D-985 and TVu 76). The plants were inoculated with Cowpea aphid-borne mosaic virus (CABMV), genus Potyvirus, Cowpea mottle virus (CMeV), genus Carmovirus and Southern bean mosaic virus (SBMV), genus Sobemovirus singly and in mixture (double and triple) at 10, 20, and 30 days after planting (DAP). The treated plants were assessed for susceptibility to the viruses, growth, and yield. In all cases of infection, early inoculation resulted in higher disease severity compared with late infection. The virus treated cowpea plants were relatively shorter than buffer inoculated control plants except the IT81D-985 plants that were taller and produced more foliage. Single infections by CABMV, CMeV, and SBMV led to a complete loss of seeds in the three cowpea cultivars at 10 DAP; only cultivar White produced some seeds at 30 DAP. Double and triple virus infections led to a total loss of seeds in all three cowpea cultivars. None of the virus infected IITA lines produced any seeds except IT81D-985 plants co-infected with CABMV and SBMV at 30 DAP with a reduction of 80%. Overall, the commercial cultivar "White" was the least susceptible to the virus treatments and produced the most yield (flowers, pods, and seeds). CABMV was the most aggressive of these viruses and early single inoculations with this virus resulted in the premature death of some of the seedlings. The presence of the Potyvirus, CABMV in the double virus infections did not appear to increase disease severity or yield loss. There was no strong evidence for synergistic interactions between the viruses in the double virus mixtures. PMID:26483824

  4. Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins.

    PubMed

    Teytelman, Leonid; Thurtle, Deborah M; Rine, Jasper; van Oudenaarden, Alexander

    2013-11-12

    Chromatin immunoprecipitation (ChIP) is the gold-standard technique for localizing nuclear proteins in the genome. We used ChIP, in combination with deep sequencing (Seq), to study the genome-wide distribution of the Silent information regulator (Sir) complex in Saccharomyces cerevisiae. We analyzed ChIP-Seq peaks of the Sir2, Sir3, and Sir4 silencing proteins and discovered 238 unexpected euchromatic loci that exhibited enrichment of all three. Surprisingly, published ChIP-Seq datasets for the Ste12 transcription factor and the centromeric Cse4 protein indicated that these proteins were also enriched in the same euchromatic regions with the high Sir protein levels. The 238 loci, termed "hyper-ChIPable", were in highly expressed regions with strong polymerase II and polymerase III enrichment signals, and the correlation between transcription level and ChIP enrichment was not limited to these 238 loci but extended genome-wide. The apparent enrichment of various proteins at hyper-ChIPable loci was not a consequence of artifacts associated with deep sequencing methods, as confirmed by ChIP-quantitative PCR. The localization of unrelated proteins, including the entire silencing complex, to the most highly transcribed genes was highly suggestive of a technical issue with the immunoprecipitations. ChIP-Seq on chromatin immunoprecipitated with a nuclear-localized GFP reproduced the above enrichment in an expression-dependent manner: induction of the GAL genes resulted in an increased ChIP signal of the GFP protein at these loci, with presumably no biological relevance. Whereas ChIP is a broadly valuable technique, some published conclusions based upon ChIP procedures may merit reevaluation in light of these findings.

  5. X-linked mental retardation: Linkage results in five unrelated families

    SciTech Connect

    Moraine, C.L.; Dessay, B.; Toutain, A.

    1994-09-01

    X-linked mental retardations are a very common cause of mental deficiency in males. Combined clinical and linkage studies in great families can help to distinguish between particular pathologies in this very heterogenous group. In five unrelated families, we have assigned the corresponding genes to Xp22.2-p21.2 for family 1, Xp21.2-p11.21 for family 2, Xp11.4-p11.23 for family 3, Xq12 for family 4, and Xq28.5-pter for family 5, respectively. Clinical features were characterized by severe hypotonia with seizures and distinctive facies (family 1), hypotonia and hypoactivity with severe mental deficiency but absence of neurological signs (family 2), neonatal hypotonia with poor sucking and moderate intrauterine growth retardation (family 3), severe neonatal hypotonia with visual impairment and profound mental deficiency and seizures (family 4), and non-specific moderate mental deficiency (family 5). These results confirm the frequent gene localizations in Xq28 and in the pericentromeric region. But more precise clinical description of so-called non-specific X-linked mental retardations is necessary (especially for the natural history of mental deficiency) with the intention to associate several families in a unique linkage study. However, the recent description of different clinical patterns in three families with mutation in the L1CAM gene suggests that allelism may be more frequent than expected, that the real number of X-L.M.R. genes could be less important than previously reported, and that testing of candidate genes by mRNA or genomic DNA studies appears as a necessary step.

  6. Molecular cytogenetic and phenotypic characterization of ring chromosome 13 in three unrelated patients

    PubMed Central

    Abdallah-Bouhjar, Inesse B.; Mougou-Zerelli, Soumaya; Hannachi, Hanene; Gmidène, Abir; Labalme, Audrey; Soyah, Najla; Sanlaville, Damien; Saad, Ali; Elghezal, Hatem

    2013-01-01

    We report on the cytogenetic and molecular investigations of constitutional de-novo ring chromosome 13s in three unrelated patients for better understanding and delineation of the phenotypic variability characterizing this genomic rearrangement. The patient’s karyotypes were as follows: 46,XY,r(13)(p11q34) dn for patients 1 and 2 and 46,XY,r(13)(p11q14) dn for patient 3, as a result of the deletion in the telomeric regions of chromosome 13. The patients were, therefore, monosomic for the segment 13q34 → 13qter; in addition, for patient 3, the deletion was larger, encompassing the segment 13q14 → 13qter. Fluorescence in situ hybridization confirmed these rearrangement and array CGH technique showed the loss of at least 2.9 Mb on the short arm and 4.7 Mb on the long arm of the chromosome 13 in patient 2. Ring chromosome 13 (r(13)) is associated with several phenotypic features like intellectual disability, marked short stature, brain and heart defects, microcephaly and genital malformations in males, including undescended testes and hypospadias. However, the hearing loss and speech delay that were found in our three patients have rarely been reported with ring chromosome 13. Although little is known about its etiology, there is interesting evidence for a genetic cause for the ring chromosome 13. We thus performed a genotype-phenotype correlation analysis to ascertain the contribution of ring chromosome 13 to the clinical features of our three cases. PMID:27625853

  7. Additive interactions of unrelated viruses in mixed infections of cowpea (Vigna unguiculata L. Walp).

    PubMed

    Nsa, Imade Y; Kareem, Kehinde T

    2015-01-01

    This study was carried out to determine the effects of single infections and co-infections of three unrelated viruses on three cowpea cultivars (one commercial cowpea cultivar "White" and 2 IITA lines; IT81D-985 and TVu 76). The plants were inoculated with Cowpea aphid-borne mosaic virus (CABMV), genus Potyvirus, Cowpea mottle virus (CMeV), genus Carmovirus and Southern bean mosaic virus (SBMV), genus Sobemovirus singly and in mixture (double and triple) at 10, 20, and 30 days after planting (DAP). The treated plants were assessed for susceptibility to the viruses, growth, and yield. In all cases of infection, early inoculation resulted in higher disease severity compared with late infection. The virus treated cowpea plants were relatively shorter than buffer inoculated control plants except the IT81D-985 plants that were taller and produced more foliage. Single infections by CABMV, CMeV, and SBMV led to a complete loss of seeds in the three cowpea cultivars at 10 DAP; only cultivar White produced some seeds at 30 DAP. Double and triple virus infections led to a total loss of seeds in all three cowpea cultivars. None of the virus infected IITA lines produced any seeds except IT81D-985 plants co-infected with CABMV and SBMV at 30 DAP with a reduction of 80%. Overall, the commercial cultivar "White" was the least susceptible to the virus treatments and produced the most yield (flowers, pods, and seeds). CABMV was the most aggressive of these viruses and early single inoculations with this virus resulted in the premature death of some of the seedlings. The presence of the Potyvirus, CABMV in the double virus infections did not appear to increase disease severity or yield loss. There was no strong evidence for synergistic interactions between the viruses in the double virus mixtures.

  8. Additive interactions of unrelated viruses in mixed infections of cowpea (Vigna unguiculata L. Walp)

    PubMed Central

    Nsa, Imade Y.; Kareem, Kehinde T.

    2015-01-01

    This study was carried out to determine the effects of single infections and co-infections of three unrelated viruses on three cowpea cultivars (one commercial cowpea cultivar “White” and 2 IITA lines; IT81D-985 and TVu 76). The plants were inoculated with Cowpea aphid-borne mosaic virus (CABMV), genus Potyvirus, Cowpea mottle virus (CMeV), genus Carmovirus and Southern bean mosaic virus (SBMV), genus Sobemovirus singly and in mixture (double and triple) at 10, 20, and 30 days after planting (DAP). The treated plants were assessed for susceptibility to the viruses, growth, and yield. In all cases of infection, early inoculation resulted in higher disease severity compared with late infection. The virus treated cowpea plants were relatively shorter than buffer inoculated control plants except the IT81D-985 plants that were taller and produced more foliage. Single infections by CABMV, CMeV, and SBMV led to a complete loss of seeds in the three cowpea cultivars at 10 DAP; only cultivar White produced some seeds at 30 DAP. Double and triple virus infections led to a total loss of seeds in all three cowpea cultivars. None of the virus infected IITA lines produced any seeds except IT81D-985 plants co-infected with CABMV and SBMV at 30 DAP with a reduction of 80%. Overall, the commercial cultivar “White” was the least susceptible to the virus treatments and produced the most yield (flowers, pods, and seeds). CABMV was the most aggressive of these viruses and early single inoculations with this virus resulted in the premature death of some of the seedlings. The presence of the Potyvirus, CABMV in the double virus infections did not appear to increase disease severity or yield loss. There was no strong evidence for synergistic interactions between the viruses in the double virus mixtures. PMID:26483824

  9. Conducting a thermal conductivity survey

    NASA Technical Reports Server (NTRS)

    Allen, P. B.

    1985-01-01

    A physically transparent approximate theory of phonon decay rates is presented starting from a pair potential model of the interatomic forces in an insulator or semiconductor. The theory applies in the classical regime and relates the 3-phonon decay rate to the third derivative of the pair potential. Phonon dispersion relations do not need to be calculated, as sum rules relate all the needed quantities directly to the pair potential. The Brillouin zone averaged phonon lifetime turns out to involve a dimensionless measure of the anharmonicity multiplied by an effective density of states for 3-phonon decay. Results are given for rare gas and alkali halide crystals. For rare gases, the results are in good agreement with more elaborate perturbation calculations. Comparison to experimental data on phonon linewidths and thermal conductivity are made.

  10. A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial.

    PubMed

    Koreth, John; Kim, Haesook T; Lange, Paulina B; Bindra, Bhavjot; Reynolds, Carol G; Chammas, Marie J; Armand, Philippe; Cutler, Corey S; Ho, Vincent T; Glotzbecker, Brett; Nikiforow, Sarah; Ritz, Jerome; Blazar, Bruce R; Soiffer, Robert J; Antin, Joseph H; Alyea, Edwin P

    2015-11-01

    Hematopoietic stem cell transplantation (HSCT) recipients lacking HLA-matched related donors have increased graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). Bortezomib added to reduced-intensity conditioning can offer benefit in T cell-replete HLA-mismatched HSCT and may also benefit myeloablative conditioning (MAC) transplants. We conducted a phase II trial of short-course bortezomib plus standard tacrolimus/methotrexate after busulfan/fludarabine MAC in 34 patients with predominantly myeloid malignancies. Fourteen (41%) received 8/8 HLA-matched unrelated donor (MUD) and 20 (59%) received 7/8 HLA-mismatched related/unrelated donor peripheral blood stem cell grafts. Median age was 49 years (range, 21 to 60), and median follow-up was 25 months (range, 11 to 36). The regimen was well tolerated. No dose modifications were required. Neutrophil and platelet engraftment occurred at a median of 14 (range, 10 to 33) and 17 (range, 10 to 54) days, respectively. Median 30-day donor chimerism was 99% (range, 90 to 100), and 100-day grades II to IV and III to IV acute GVHD incidence was 32% and 12% respectively. One-year chronic GVHD incidence was 50%. Two-year cumulative incidence of both NRM and relapse was 16%. Two-year progression-free and overall survival rates were 70% and 71%, respectively. Outcomes were comparable to an 8/8 MUD MAC cohort (n = 45). Immune reconstitution was robust. Bortezomib-based MAC HSCT is well tolerated, with HLA-mismatched outcomes comparable with 8/8 MUD MAC HSCT, and is suitable for randomized evaluation. (clinicaltrials.gov: NCT01323920.).

  11. Multi-ion conduction bands in a simple model of calcium ion channels

    NASA Astrophysics Data System (ADS)

    Kaufman, I.; Luchinsky, D. G.; Tindjong, R.; McClintock, P. V. E.; Eisenberg, R. S.

    2013-04-01

    We report self-consistent Brownian dynamics simulations of a simple electrostatic model of the selectivity filters (SF) of calcium ion channels. They reveal regular structure in the conductance and selectivity as functions of the fixed negative charge Qf at the SF. With increasing Qf, there are distinct regions of high conductance (conduction bands) M0, M1, M2 separated by regions of almost zero-conductance (stop-bands). Two of these conduction bands, M1 and M2, are related to the saturated calcium occupancies of P = 1 and P = 2, respectively and demonstrate self-sustained conductivity. Despite the model's limitations, its M1 and M2 bands show high calcium selectivity and prominent anomalous mole fraction effects and can be identified with the L-type and RyR calcium channels. The non-selective band M0 can be identified with a non-selective cation channel, or with OmpF porin.

  12. Functional expression of the hyperpolarization-activated, non-selective cation current If in immortalized HL-1 cardiomyocytes

    PubMed Central

    Sartiani, Laura; Bochet, Pascal; Cerbai, Elisabetta; Mugelli, Alessandro; Fischmeister, Rodolphe

    2002-01-01

    HL-1 cells are adult mouse atrial myocytes induced to proliferate indefinitely by SV40 large T antigen. These cells beat spontaneously when confluent and express several adult cardiac cell markers including the outward delayed rectifier K+ channel. Here, we examined the presence of a hyperpolarization-activated If current in HL-1 cells using the whole-cell patch-clamp technique on isolated cells enzymatically dissociated from the culture at confluence. Cell membrane capacitance (Cm) ranged from 5 to 53 pF. If was detected in about 30 % of the cells and its occurrence was independent of the stage of the culture. If maximal slope conductance was 89.7 ± 0.4 pS pF−1 (n = 10). If current in HL-1 cells showed typical characteristics of native cardiac If current: activation threshold between −50 and −60 mV, half-maximal activation potential of −83.1 ± 0.7 mV (n = 50), reversal potential at −20.8 ± 1.5 mV (n = 10), time-dependent activation by hyperpolarization and blockade by 4 mm Cs+. In half of the cells tested, activation of adenylyl cyclase by the forskolin analogue L858051 (20 μm) induced both a ≈6 mV positive shift of the half-activation potential and a ≈37 % increase in the fully activated If current. RT-PCR analysis of the hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) expressed in HL-1 cells demonstrated major contributions of HCN1 and HCN2 channel isoforms to If current. Cytosolic Ca2+ oscillations in spontaneously beating HL-1 cells were measured in Fluo-3 AM-loaded cells using a fast-scanning confocal microscope. The oscillation frequency ranged from 1.3 to 5 Hz and the spontaneous activity was stopped in the presence of 4 mm Cs+. Action potentials from HL-1 cells had a triangular shape, with an overshoot at +15 mV and a maximal diastolic potential of −69 mV, i.e. more negative than the threshold potential for If activation. In conclusion, HL-1 cells display a hyperpolarization-activated If current which might

  13. 26 CFR 1.513-1 - Definition of unrelated trade or business.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... stand by a hospital auxiliary for only 2 weeks at a state fair would not be the regular conduct of trade... films in connection with its program of public education in the arts and sciences. The theater is...

  14. 26 CFR 1.513-1 - Definition of unrelated trade or business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... stand by a hospital auxiliary for only 2 weeks at a state fair would not be the regular conduct of trade... films in connection with its program of public education in the arts and sciences. The theater is...

  15. 26 CFR 1.513-1 - Definition of unrelated trade or business.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... stand by a hospital auxiliary for only 2 weeks at a state fair would not be the regular conduct of trade... films in connection with its program of public education in the arts and sciences. The theater is...

  16. 26 CFR 1.513-1 - Definition of unrelated trade or business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... stand by a hospital auxiliary for only 2 weeks at a state fair would not be the regular conduct of trade... films in connection with its program of public education in the arts and sciences. The theater is...

  17. Macrosomia, obesity, macrocephaly and ocular abnormalities (MOMO syndrome) in two unrelated patients: delineation of a newly recognized overgrowth syndrome.

    PubMed

    Moretti-Ferreira, D; Koiffmann, C P; Listik, M; Setian, N; Wajntal, A

    1993-06-15

    We describe 2 unrelated patients, a boy and a girl, with an overgrowth syndrome and the following common characteristics: macrocrania, obesity, ocular abnormalities (retinal coloboma and nystagmus), downward slant of palpebral fissures, mental retardation, and delayed bone maturation. Both cases are of sporadic occurrence with no consanguinity between the parents. We suggest that this syndrome is due to a new autosomal dominant mutation and propose to designate it with the acronym of "MOMO syndrome" (Macrosomia, Obesity, Macrocrania, Ocular anomalities.

  18. Common trade-offs between xylem resistance to cavitation and other physiological traits do not hold among unrelated Populus deltoides x Populus nigra hybrids.

    PubMed

    Fichot, Régis; Barigah, Têtè S; Chamaillard, Sylvain; LE Thiec, Dider; Laurans, Françoise; Cochard, Hervé; Brignolas, Franck

    2010-09-01

    We examined the relationships between xylem resistance to cavitation and 16 structural and functional traits across eight unrelated Populus deltoides x Populus nigra genotypes grown under two contrasting water regimes. The xylem water potential inducing 50% loss of hydraulic conductance (Psi(50)) varied from -1.60 to -2.40 MPa. Drought-acclimated trees displayed a safer xylem, although the extent of the response was largely genotype dependent, with Psi(50) being decreased by as far as 0.60 MPa. At the tissue level, there was no clear relationship between xylem safety and either xylem water transport efficiency or xylem biomechanics; the only structural trait to be strongly associated with Psi(50) was the double vessel wall thickness, genotypes exhibiting a thicker double wall being more resistant. At the leaf level, increased cavitation resistance was associated with decreased stomatal conductance, while no relationship could be identified with traits associated with carbon uptake or bulk leaf carbon isotope discrimination, a surrogate of intrinsic water-use efficiency. At the whole-plant level, increased safety was associated with higher shoot growth potential under well-irrigated regime only. We conclude that common trade-offs between xylem resistance to cavitation and other physiological traits that are observed across species may not necessarily hold true at narrower scales.

  19. Using ancestry matching to combine family-based and unrelated samples for genome-wide association studies.

    PubMed

    Crossett, Andrew; Kent, Brian P; Klei, Lambertus; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn; Devlin, Bernie

    2010-12-10

    We propose a method to analyze family-based samples together with unrelated cases and controls. The method builds on the idea of matched case-control analysis using conditional logistic regression (CLR). For each trio within the family, a case (the proband) and matched pseudo-controls are constructed, based upon the transmitted and untransmitted alleles. Unrelated controls, matched by genetic ancestry, supplement the sample of pseudo-controls; likewise unrelated cases are also paired with genetically matched controls. Within each matched stratum, the case genotype is contrasted with control/pseudo-control genotypes via CLR, using a method we call matched-CLR (mCLR). Eigenanalysis of numerous SNP genotypes provides a tool for mapping genetic ancestry. The result of such an analysis can be thought of as a multidimensional map, or eigenmap, in which the relative genetic similarities and differences amongst individuals is encoded in the map. Once constructed, new individuals can be projected onto the ancestry map based on their genotypes. Successful differentiation of individuals of distinct ancestry depends on having a diverse, yet representative sample from which to construct the ancestry map. Once samples are well-matched, mCLR yields comparable power to competing methods while ensuring excellent control over Type I error.

  20. Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid.

    PubMed

    Di Genova, Gianfranco; Savelyeva, Natalia; Suchacki, Amy; Thirdborough, Stephen M; Stevenson, Freda K

    2010-04-01

    Antigen-specific CD4(+) T cells are central to natural and vaccine-induced immunity. An ongoing antigen-specific T-cell response can, however, influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated whether boosting memory CD4(+) T cells against TT in vivo would influence injected CD4(+) TCR transgenic T cells (OT-II) specific for an unrelated OVA peptide. If OT-II cells were pre-activated with OVA peptide in vitro, these cells showed a bystander proliferative response during the ongoing parallel TT-specific response. Bystander proliferation was dependent on boosting of the TT-specific memory response in the recipients, with no effect in naive mice. Bystander stimulation was also proportional to the strength of the TT-specific memory T-cell response. T cells activated in vitro displayed functional receptors for IL-2 and IL-7, suggesting these as potential mediators. This crosstalk between a stimulated CD4(+) memory T-cell response and CD4(+) T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens.

  1. Cytosolic PTEN-induced Putative Kinase 1 Is Stabilized by the NF-κB Pathway and Promotes Non-selective Mitophagy.

    PubMed

    Lim, Grace G Y; Chua, Doreen S K; Basil, Adeline H; Chan, Hui-Ying; Chai, Chou; Arumugam, Thiruma; Lim, Kah-Leong

    2015-07-01

    The potential cellular function of the 53-kDa cytosolic form of PINK1 (PINK1-53) is often overlooked because of its rapid degradation by the proteasome upon its production. Although a number of recent studies have suggested various roles for PINK1-53, how this labile PINK1 species attains an adequate expression level to fulfil these roles remains unclear. Here we demonstrated that PINK1-53 is stabilized in the presence of enhanced Lys-63-linked ubiquitination and identified TRAF6-related NF-κB activation as a novel pathway involved in this. We further showed that a mimetic of PINK1-53 promotes mitophagy but, curiously, in apparently healthy mitochondria. We speculate that this "non-selective" form of mitophagy may potentially help to counteract the build-up of reactive oxygen species in cells undergoing oxidative stress and, as such, represent a cytoprotective response.

  2. Molecular evolution of calcification genes in morphologically similar but phylogenetically unrelated scleractinian corals.

    PubMed

    Wirshing, Herman H; Baker, Andrew C

    2014-08-01

    Molecular phylogenies of scleractinian corals often fail to agree with traditional phylogenies derived from morphological characters. These discrepancies are generally attributed to non-homologous or morphologically plastic characters used in taxonomic descriptions. Consequently, morphological convergence of coral skeletons among phylogenetically unrelated groups is considered to be the major evolutionary process confounding molecular and morphological hypotheses. A strategy that may help identify cases of convergence and/or diversification in coral morphology is to compare phylogenies of existing "neutral" genetic markers used to estimate genealogic phylogenetic history with phylogenies generated from non-neutral genes involved in calcification (biomineralization). We tested the hypothesis that differences among calcification gene phylogenies with respect to the "neutral" trees may represent convergent or divergent functional strategies among calcification gene proteins that may correlate to aspects of coral skeletal morphology. Partial sequences of two nuclear genes previously determined to be involved in the calcification process in corals, "Cnidaria-III" membrane-bound/secreted α-carbonic anhydrase (CIII-MBSα-CA) and bone morphogenic protein (BMP) 2/4, were PCR-amplified, cloned and sequenced from 31 scleractinian coral species in 26 genera and 9 families. For comparison, "neutral" gene phylogenies were generated from sequences from two protein-coding "non-calcification" genes, one nuclear (β-tubulin) and one mitochondrial (cytochrome b), from the same individuals. Cloned CIII-MBSα-CA sequences were found to be non-neutral, and phylogenetic analyses revealed CIII-MBSα-CAs to exhibit a complex evolutionary history with clones distributed between at least 2 putative gene copies. However, for several coral taxa only one gene copy was recovered. With CIII-MBSα-CA, several recovered clades grouped taxa that differed from the "non-calcification" loci. In some

  3. Molecular evolution of calcification genes in morphologically similar but phylogenetically unrelated scleractinian corals.

    PubMed

    Wirshing, Herman H; Baker, Andrew C

    2014-08-01

    Molecular phylogenies of scleractinian corals often fail to agree with traditional phylogenies derived from morphological characters. These discrepancies are generally attributed to non-homologous or morphologically plastic characters used in taxonomic descriptions. Consequently, morphological convergence of coral skeletons among phylogenetically unrelated groups is considered to be the major evolutionary process confounding molecular and morphological hypotheses. A strategy that may help identify cases of convergence and/or diversification in coral morphology is to compare phylogenies of existing "neutral" genetic markers used to estimate genealogic phylogenetic history with phylogenies generated from non-neutral genes involved in calcification (biomineralization). We tested the hypothesis that differences among calcification gene phylogenies with respect to the "neutral" trees may represent convergent or divergent functional strategies among calcification gene proteins that may correlate to aspects of coral skeletal morphology. Partial sequences of two nuclear genes previously determined to be involved in the calcification process in corals, "Cnidaria-III" membrane-bound/secreted α-carbonic anhydrase (CIII-MBSα-CA) and bone morphogenic protein (BMP) 2/4, were PCR-amplified, cloned and sequenced from 31 scleractinian coral species in 26 genera and 9 families. For comparison, "neutral" gene phylogenies were generated from sequences from two protein-coding "non-calcification" genes, one nuclear (β-tubulin) and one mitochondrial (cytochrome b), from the same individuals. Cloned CIII-MBSα-CA sequences were found to be non-neutral, and phylogenetic analyses revealed CIII-MBSα-CAs to exhibit a complex evolutionary history with clones distributed between at least 2 putative gene copies. However, for several coral taxa only one gene copy was recovered. With CIII-MBSα-CA, several recovered clades grouped taxa that differed from the "non-calcification" loci. In some

  4. Unrelated bone marrow transplantation for beta-thalassemia patients: The experience of the Italian Bone Marrow Transplant Group.

    PubMed

    La Nasa, Giorgio; Argiolu, Franca; Giardini, Claudio; Pession, Andrea; Fagioli, Franca; Caocci, Giovanni; Vacca, Adriana; De Stefano, Piero; Piras, Eugenia; Ledda, Antonio; Piroddi, Antonio; Littera, Roberto; Nesci, Sonia; Locatelli, Franco

    2005-01-01

    Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA-matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty-three males and 35 females (age range, 2-37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high-resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant-related causes. Grade II-IV acute graft-versus-host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67-88%), whereas the Kaplan-Meier estimates of disease-free survival (DFS) with transfusion independence was 65.8% (CI 54-77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90-100%) and 80.0% (CI 65-94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49-80%) and DFS was 54.5% (CI 38-70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling. PMID:16339665

  5. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation.

    PubMed

    Crocchiolo, Roberto; Zino, Elisabetta; Vago, Luca; Oneto, Rosi; Bruno, Barbara; Pollichieni, Simona; Sacchi, Nicoletta; Sormani, Maria Pia; Marcon, Jessica; Lamparelli, Teresa; Fanin, Renato; Garbarino, Lucia; Miotti, Valeria; Bandini, Giuseppe; Bosi, Alberto; Ciceri, Fabio; Bacigalupo, Andrea; Fleischhauer, Katharina

    2009-08-13

    The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for oncohematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher Kaplan-Meier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors. PMID:19515726

  6. Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

    PubMed Central

    Hollenbach, Jill A.; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J.; Maiers, Martin

    2015-01-01

    We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals. PMID:26287376

  7. Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics.

    PubMed

    Hollenbach, Jill A; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J; Maiers, Martin

    2015-01-01

    We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents' information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

  8. Chronic Periprosthetic Hip Joint Infection. A Retrospective, Observational Study on the Treatment Strategy and Prognosis in 130 Non-Selected Patients

    PubMed Central

    Troelsen, Anders; Søballe, Kjeld

    2016-01-01

    Introduction Limited information is available regarding the treatment strategy and prognosis of non-selected patients treated for chronic periprosthetic hip joint infection. Such information is important as no head-to-head studies on treatment strategies are available. The purpose of this study is to report on the treatment strategy and prognosis of a non-selected, consecutive patient population Methods We identified 130 patients in the National Patient Registry, consecutively treated for a chronic periprosthetic hip joint infection between 2003–2008 at 11 departments of orthopaedic surgery. We extracted information regarding patient demographics, treatment and outcome. 82 patients were re-implanted in a two-stage revision (national standard), the remaining 48 were not re-implanted in a two-stage revision. We were able to collect up-to-date information on all patients to date of death or medical chart review with a minimum of 5 years follow-up by the nationwide electronic patient record system Results After primary revision surgery, 53 patients (41%) had a spacer in situ, 64 (50%) had a resection arthroplasty and 13 (9%) did not have the infected implant removed. 63% were re-implanted in a two-stage revision. Re-implantation was performed after an interim period of 14 weeks (IQR 10–18). Patients re-implanted were younger (p-value 0.0006), had a lower CCS score (p-value 0.005), a lower ASA score (p-value 0.0001) and a 68% lower mortality risk in the follow-up period (p-value <0.00001). After adjusting for selected confounders, the mortality risk was no longer significantly different. The 5-year re-infection rate after re-implantation was 14.6% (95%CI 8.0–23.1). Re-infections occurred mainly within 3 years of follow-up. The overall 1-year survival rate was 92% (95%CI 86–96) and the overall 5-year survival rate was 68% (95%CI 59–75). The 5-year survival rate after a two-stage revision was 82% (95%CI 71–89) and in those not re-implanted 45% (95%CI 30–58

  9. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood

    PubMed Central

    Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter; Brunstein, Claudio; Sengeloev, Henrik; Finke, Jürgen; Mohty, Mohamad; Rio, Bernard; Petersen, Eefke; Guilhot, François; Niederwieser, Dietger; Cornelissen, Jan J.; Jindra, Pavel; Nagler, Arnon; Fegueux, Nathalie; Schoemans, Hélène; Robinson, Stephen; Ruggeri, Annalisa; Gluckman, Eliane; Canals, Carmen; Sureda, Anna

    2014-01-01

    We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P<0.0001) and chronic graft-versus-host disease (26% vs. 52%; P=0.0005) were less frequent after unrelated cord blood than after matched unrelated donor, whereas no differences were observed in grade II–IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28%), and relapse or progression (28% vs. 35%) at 36 months. There were also no significant differences in 2-year progression-free survival (43% vs. 58%, respectively) and overall survival (36% vs. 51%) at 36 months. In a multivariate analysis, no differences were observed in the outcomes between the two stem cell sources except for a higher risk of neutrophil engraftment (hazard ratio=2.12; P<0.0001) and chronic graft-versus-host disease (hazard ratio 2.10; P=0.0002) after matched unrelated donor transplant. In conclusion, there was no difference in final outcomes after transplantation between umbilical cord blood and matched unrelated donor transplant. Umbilical cord blood is a valuable alternative for patients with lymphoid malignancies lacking an HLA-matched donor, being associated with lower risk of chronic graft-versus-host disease. PMID:23935024

  10. Interleukin-1 alpha genotype and outcome of unrelated donor haematopoietic stem cell transplantation for chronic myeloid leukaemia

    PubMed Central

    Mehta, Parinda A.; Eapen, Mary; Klein, John P.; Gandham, Sharavi; Elliott, James; Zamzow, Tiffany; Combs, Michelle; Aplenc, Richard; MacMillan, Margaret L.; Weisdorf, Daniel J.; Petersdorf, Effie; Davies, Stella M.

    2010-01-01

    Summary Interleukin-1 alpha (IL-1α) is a pro-inflammatory cytokine that is implicated in the initiation/maintenance of graft-versus-host disease (GVHD) and the immune response to infection. A cytosine (C) to thymine (T) transition at position −889 is believed to influence gene transcription. A previous single institution study showed that the presence of at least one IL1A T allele in the donor was associated with improved survival after unrelated donor haematopoietic stem cell transplant and lower transplant-related mortality if the donor and recipient each possessed the IL1A T allele. The present study sought to confirm these results in a larger homogeneous population. Thus the study population included 426 patients older than 18 years with chronic myeloid leukaemia (CML), transplanted in first chronic phase and receiving a total body irradiation and cyclophosphamide preparative regimen. Donor recipient pairs were categorised into four groups according to the presence or absence of an IL1A T allele in the donor and recipient. There were no significant differences in patient, donor and transplant characteristics between the groups. We did not observe an association with IL-1α genotype in donor and/or recipient and transplant-outcome. These data suggest that the outcome of unrelated donor transplant for CML is not influenced by IL-1α genotype. PMID:17391495

  11. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia

    PubMed Central

    Cooley, Sarah; Weisdorf, Daniel J.; Guethlein, Lisbeth A.; Klein, John P.; Wang, Tao; Le, Chap T.; Marsh, Steven G. E.; Geraghty, Daniel; Spellman, Stephen; Haagenson, Michael D.; Ladner, Martha; Trachtenberg, Elizabeth; Parham, Peter

    2010-01-01

    Killer-cell immunoglobulin-like receptor (KIR) genes form a diverse, immunogenetic system. Group A and B KIR haplotypes have distinctive centromeric (Cen) and telomeric (Tel) gene-content motifs. Aiming to develop a donor selection strategy to improve transplant outcome, we compared the contribution of these motifs to the clinical benefit conferred by B haplotype donors. We KIR genotyped donors from 1409 unrelated transplants for acute myelogenous leukemia (AML; n = 1086) and acute lymphoblastic leukemia (ALL; n = 323). Donor KIR genotype influenced transplantation outcome for AML but not ALL. Compared with A haplotype motifs, centromeric and telomeric B motifs both contributed to relapse protection and improved survival, but Cen-B homozygosity had the strongest independent effect. With Cen-B/B homozygous donors the cumulative incidence of relapse was 15.4% compared with 36.5% for Cen-A/A donors (relative risk of relapse 0.34; 95% confidence interval 0.2-0.57; P < .001). Overall, significantly reduced relapse was achieved with donors having 2 or more B gene-content motifs (relative risk 0.64; 95% confidence interval 0.48-0.86; P = .003) for both HLA-matched and mismatched transplants. KIR genotyping of several best HLA-matched potential unrelated donors should substantially increase the frequency of transplants by using grafts with favorable KIR gene content. Adopting this practice could result in superior disease-free survival for patients with AML. PMID:20581313

  12. Array-Based Gene Discovery with Three Unrelated Subjects Shows SCARB2/LIMP-2 Deficiency Causes Myoclonus Epilepsy and Glomerulosclerosis

    PubMed Central

    Berkovic, Samuel F.; Dibbens, Leanne M.; Oshlack, Alicia; Silver, Jeremy D.; Katerelos, Marina; Vears, Danya F.; Lüllmann-Rauch, Renate; Blanz, Judith; Zhang, Ke Wei; Stankovich, Jim; Kalnins, Renate M.; Dowling, John P.; Andermann, Eva; Andermann, Frederick; Faldini, Enrico; D'Hooge, Rudi; Vadlamudi, Lata; Macdonell, Richard A.; Hodgson, Bree L.; Bayly, Marta A.; Savige, Judy; Mulley, John C.; Smyth, Gordon K.; Power, David A.; Saftig, Paul; Bahlo, Melanie

    2008-01-01

    Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies. PMID:18308289

  13. The Role of Speech Therapy in Patients Who Underwent Laryngeal Microsurgery due to Phonotraumatic Lesions and Lesions Unrelated to Phonotrauma

    PubMed Central

    Macedo, Claudia de Assis Corrêa de; Macedo, Evaldo Dacheux de; Malafaia, Osvaldo; Catani, Guilherme Simas do Amaral; Ido, Jorge Massaki; Stahlke, Henrique Jorge

    2014-01-01

    Introduction The role of the speech-language pathology in the multiprofessional team dealing with laryngology and the voice has been recognized for a long time. Scientific studies in this field recommend therapies for laryngeal microsurgeries; few of the studies, however, effectively evaluate the result of postoperative speech therapy. Objective To compare speech therapy evaluation and treatment among patients with phonotraumatic lesions and patients with lesions unrelated to phonotrauma who underwent laryngeal microsurgery. Methods This study was performed at IPO Hospital (Paranaense Institute of Otorhinolaryngology, Curitiba, Paraná, Brazil) between February 2010 and February 2011. Of 254 patients who underwent laryngeal microsurgery, 208 patients were included in the study and divided in two groups: group A with phonotraumatic lesions (n = 131) and group B with lesions unrelated to phonotrauma (n = 77). The number of sessions and the functional result after speech therapy were evaluated. Results The number of postoperative phonotherapy sessions after microsurgery was up to 10 sessions in 89.31% and 87.71% for groups A and B, respectively. Phonotherapy treatment showed a better functional evolution in group A (92.37%). Conclusion A significant difference was observed only in functional evolution, which was better in the group with phonotraumatic lesions (p < 0.0001). PMID:25992078

  14. Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial.

    PubMed

    Jubert, C; Wall, D A; Grimley, M; Champagne, M A; Duval, M

    2011-02-01

    Relapsed or refractory neuroblastoma is uniformly fatal. We hypothesized that allogeneic response could provide a platform for immunotherapy in neuroblastoma. We therefore undertook a pilot trial of unrelated cord blood transplantation after reduced intensity conditioning regimen (RIC) in children with relapsed neuroblastoma to assess engraftment and tolerability in this heavily pretreated population. The RIC included CY (50 mg/kg, day -6), fludarabine (40 mg/m(2), days -6 to -2), total body irradiation (200 cGy, day -1), and rabbit anti-thymocyte globulin (2.5 mg/kg, days -3 to -1). Six patients were enrolled: four were in partial responsive relapse, one with a mixed response and one in refractory relapse. All patients tolerated the regimen well and had donor engraftment with full neutrophil and plt recovery (median time 12 and 35 days, respectively). One patient never experienced neutropenia and another did not need plt transfusions. All patients progressed after transplant (median time 55 days, 26-180 days). Natural killer (NK) cell counts were normal within 2 months, whereas T-cell recovery was slower. In conclusion, unrelated cord blood engrafts after RIC in children with refractory neuroblastoma. Future research should be aimed at transplanting patients with minimal residual disease, using less intensive immunosuppression and adding NK-cell based post transplant immunotherapy.

  15. Phallometric comparison of pedophilic interest in nonadmitting sexual offenders against stepdaughters, biological daughters, other biologically related girls, and unrelated girls.

    PubMed

    Blanchard, Ray; Kuban, Michael E; Blak, Thomas; Cantor, James M; Klassen, Philip; Dickey, Robert

    2006-01-01

    This study compared the mean levels of sexual response to children produced by four groups of men with sexual offences against prepubescent girls and two comparison groups with other offences or no offences. All groups (N = 291) consisted of patients referred for clinical assessment of their sexual behavior or interests. Group assignment was determined by the victim's age and her relation to the patient: biological daughter; stepdaughter; other biologically related girl (e.g., sister, niece, granddaughter); unrelated girl; adult woman; and no known victim. The men with sexual offences had precisely one known victim each. The patients with offences may or may not have denied the act of which they were accused, but all patients denied an erotic preference for children. Sexual response to children was assessed by means of phallometric testing, a psychophysiological technique in which the individual's penile blood volume is monitored while he is presented with a standardized set of laboratory stimuli depicting male and female children and adults. The results indicated that the mean level of pedophilic response in men with offences against daughters or stepdaughters is intermediate between that in men with offences against otherwise-related or unrelated girls and that in men with no offences against girls at all. PMID:16598663

  16. The logistic regression model for gene-environment interactions using both case-parent trios and unrelated case-controls.

    PubMed

    Guo, Chao-Yu; Chen, Yu-Jing; Chen, Yi-Hau

    2014-07-01

    One of the greatest challenges in genetic studies is the determination of gene-environment interactions due to underlying complications and inadequate statistical power. With the increased sample size gained by using case-parent trios and unrelated cases and controls, the performance may be much improved. Focusing on a dichotomous trait, a two-stage approach was previously proposed to deal with gene-environment interaction when utilizing mixed study samples. Theoretically, the two-stage association analysis uses likelihood functions such that the computational algorithms may not converge in the maximum likelihood estimation with small study samples. In an effort to avoid such convergence issues, we propose a logistic regression framework model, based on the combined haplotype relative risk (CHRR) method, which intuitively pools the case-parent trios and unrelated subjects in a two by two table. A positive feature of the logistic regression model is the effortless adjustment for either discrete or continuous covariates. According to computer simulations, under the circumstances in which the two-stage test converges in larger sample sizes, we discovered that the performances of the two tests were quite similar; the two-stage test is more powerful under the dominant and additive disease models, but the extended CHRR is more powerful under the recessive disease model. PMID:24766627

  17. Mycobacterium simiae infection in two unrelated patients with different forms of inherited IFN-γR2 deficiency

    PubMed Central

    Martínez-Barricarte, Rubén; Megged, Orli; Stepensky, Polina; Casimir, Pierre; Moncada-Velez, Marcela; Averbuch, Diana; Assous, Marc Victor; Abuzaitoun, Omar; Kong, Xiao-Fei; Pedergnana, Vincent; Deswarte, Caroline; Migaud, Mélanie; Rose-John, Stefan; Itan, Yuval; Boisson, Bertrand; Belkadi, Aziz; Conti, Francesca; Abel, Laurent; Vogt, Guillaume; Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent; Bustamante, Jacinta

    2014-01-01

    Interferon-γ receptor 2 (IFN-γR2) deficiency is a rare primary immunodeficiency characterized by predisposition to infections with weakly virulent mycobacteria, such as environmental mycobacteria and BCG vaccines. We describe here two children with IFN-γR2 deficiency, from unrelated, consanguineous kindreds of Arab and Israeli descent. The first patient was a boy who died at the age of 4.5 years, from recurrent, disseminated disease caused by Mycobacterium simiae. His IFN-γR2 defect was autosomal recessive and complete. The second patient was a girl with multiple disseminated mycobacterial infections, including infection with M. simiae. She died at the age of five years, a short time after the transplantation of umbilical cord blood cells from an unrelated donor. Her IFN-γR2 defect was autosomal recessive and partial. Autosomal recessive IFN-γR2 deficiency is life-threatening, even in its partial form, and genetic diagnosis and familial counseling are therefore particularly important for this condition. These two cases are the first of IFN-γR2 deficiency associated with M simiae infection to be described. PMID:25135595

  18. Mycobacterium simiae infection in two unrelated patients with different forms of inherited IFN-γR2 deficiency.

    PubMed

    Martínez-Barricarte, Rubén; Megged, Orli; Stepensky, Polina; Casimir, Pierre; Moncada-Velez, Marcela; Averbuch, Diana; Assous, Marc Victor; Abuzaitoun, Omar; Kong, Xiao-Fei; Pedergnana, Vincent; Deswarte, Caroline; Migaud, Mélanie; Rose-John, Stefan; Itan, Yuval; Boisson, Bertrand; Belkadi, Aziz; Conti, Francesca; Abel, Laurent; Vogt, Guillaume; Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent; Bustamante, Jacinta

    2014-11-01

    Interferon-γ receptor 2 (IFN-γR2) deficiency is a rare primary immunodeficiency characterized by predisposition to infections with weakly virulent mycobacteria, such as environmental mycobacteria and BCG vaccines. We describe here two children with IFN-γR2 deficiency, from unrelated, consanguineous kindreds of Arab and Israeli descent. The first patient was a boy who died at the age of 4.5 years, from recurrent, disseminated disease caused by Mycobacterium simiae. His IFN-γR2 defect was autosomal recessive and complete. The second patient was a girl with multiple disseminated mycobacterial infections, including infection with M. simiae. She died at the age of 5 years, a short time after the transplantation of umbilical cord blood cells from an unrelated donor. Her IFN-γR2 defect was autosomal recessive and partial. Autosomal recessive IFN-γR2 deficiency is life-threatening, even in its partial form, and genetic diagnosis and familial counseling are therefore particularly important for this condition. These two cases are the first of IFN-γR2 deficiency associated with M. simiae infection to be described. PMID:25135595

  19. Hormonal correlates of changes in interest in unrelated infants across the peripartum period in female baboons (Papio hamadryas anubis sp.).

    PubMed

    Ramirez, Stephanie M; Bardi, Massimo; French, Jeffrey A; Brent, Linda

    2004-12-01

    In past research on human and nonhuman primates, maternal responsiveness and behavior has been thought of as an experiential, cognitive mechanism; however, recent findings have shown that maternal motivation and behavior may not be entirely divorced from the endocrine system. To investigate the relationship between interest in infants and the hormonal changes related to pregnancy, we examined the nature of social interactions across parturition between a large sample (n = 133) of adult female baboons (Papio hamadryas anubis sp.) and unrelated infants. Prepartum data were collected during ten 30-min focal observations for each subject. Each mother-infant pair was then observed through the infant's first 8 weeks of life. A total of 2325 h of observation was recorded. Urine was collected on 65 subjects, starting 5 weeks before the expected date of parturition and ending 4 weeks after parturition. Evidence for a connection between endocrine function and responsiveness toward infants was found. Affiliative behaviors during the prepartum period were positively correlated to the estrogen/cortisol ratio and high dominance rank. In the postpartum period, affiliative behaviors were positively correlated with prepartum progesterone and dominance rank, and negatively correlated with postpartum cortisol levels. Finally, a positive correlation was recorded during the postpartum period between prepartum progesterone and aggression, and a negative correlation between postpartum cortisol and aggression and submission. Our data suggest that the endocrine changes that may help regulate maternal care of offspring also influence the way in which pre- and postpartum female baboons interact with unrelated infants in their social group.

  20. Toward the most ideal case-control design with related and unrelated dogs in whole-exome sequencing studies.

    PubMed

    Broeckx, B J G; Coopman, F; Verhoeven, G E C; De Keulenaer, S; De Meester, E; Bavegems, V; Smets, P; Van Ryssen, B; Van Nieuwerburgh, F; Deforce, D

    2016-04-01

    With the recent development of whole-exome sequencing enrichment designs for the dog, a novel tool for disease-association studies became available. The aim of disease-association studies is to identify one or a very limited number of putative causal variants or genes from the large pool of genetic variation. To maximize the efficiency of these studies and to provide some directions of what to expect, we evaluated the effect on variant reduction for various combinations of cases and controls for both dominant and recessive types of inheritance assuming variable degrees of penetrance and detectance. In this study, variant data of 14 dogs (13 Labrador Retrievers and one Dogue de Bordeaux), obtained by whole-exome sequencing, were analyzed. In the filtering process, we found that unrelated dogs from the same breed share up to 70% of their variants, which is likely a consequence of the breeding history of the dog. For the designs tested with unrelated dogs, combining two cases and two controls gave the best result. These results were improved further by adding closely related dogs. Reduced penetrance and/or detectance has a drastic effect on the efficiency and is likely to have a profound effect on the sample size needed to elucidate the causal variant. Overall, we demonstrated that sequencing a small number of dogs results in a marked reduction of variants that are likely sufficient to pinpoint causal variants or genes.

  1. Decision-making in adult thalassemia patients undergoing unrelated bone marrow transplantation: quality of life, communication and ethical issues.

    PubMed

    Caocci, G; Pisu, S; Argiolu, F; Giardini, C; Locatelli, F; Vacca, A; Orofino, M G; Piras, E; De Stefano, P; Addari, M C; Ledda, A; La Nasa, G

    2006-01-01

    Bone marrow transplantation (BMT) represents a potentially curative treatment of thalassemia. For patients without an HLA-identical sibling donor, recourse to an unrelated donor is a practicable option but the candidates and their families are faced with a difficult decision. They can either choose to continue the supportive therapy, with no chance of definitive cure, or they accept the mortality risk of BMT in the hope of obtaining a definitive resolution of the disease. We investigated the communication strategies and the post transplantation quality of life (QoL) in 19 adult thalassemia patients surviving after an unrelated donor BMT. The patients were given two questionnaires: a questionnaire to evaluate pre-transplantation communication factors and the EORTC QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the communication modalities employed by the physicians. The global post transplantation QoL in our patient cohort was found to be good. The approach used in this study may offer a contribution to understanding the decision-making process leading to the choice of a treatment with a high mortality risk for a chronic, non-malignant disease. Finally, some ethical issues of this therapeutic approach are briefly addressed. PMID:16299541

  2. CASEIN KINASE-MEDIATED PHOSPHORYLATION OF SERINE 839 IS NECESSARY FOR BASOLATERAL LOCALIZATION OF THE Ca2+-ACTIVATED NON-SELECTIVE CATION CHANNEL TRPM4

    PubMed Central

    Cerda, Oscar; Cáceres, Mónica; Park, Kang-Sik; Leiva-Salcedo, Elías; Romero, Aníbal; Varela, Diego

    2014-01-01

    TRPM4 is a Ca2+-activated non-selective cation channel expressed in a wide range of human tissues. TRPM4 participates in a variety of physiological processes such as T cell activation, myogenic vasoconstriction and allergic reactions. TRPM4 Ca2+ sensitivity is enhanced by calmodulin (CaM) and phosphathydilinositol 4, 5-biphosphate (PI(4,5)P2) binding, as well as, under certain conditions, PKC activation. However, information as to the mechanisms of modulation of this channel remain unknown, including direct identification of phosphorylation sites on TRPM4 and their role in channel features. Here, we use mass-spectrometric-based proteomic approaches (immunoprecipitation and tandem mass spectrometry), to unambiguously identify S839 as a phosphorylation site present on human TRPM4 expressed in a human cell line. Site-directed mutagenesis employing a serine to alanine mutation to eliminate phosphorylation, and a phospho-mimetic aspartate mutation, as well as biochemical and immunocytochemical experiments, revealed a role for S839 phosphorylation in the basolateral expression of TRPM4 channels in epithelial cells. Moreover, we demonstrated that casein kinase 1 (CK1) phosphorylates S839 and is responsible for the basolateral localization of TRPM4. PMID:25231975

  3. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis.

    PubMed

    Chen, Xin; He, Wan-Ting; Hu, Lichen; Li, Jingxian; Fang, Yuan; Wang, Xin; Xu, Xiaozheng; Wang, Zhuo; Huang, Kai; Han, Jiahuai

    2016-09-01

    Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis. PMID:27573174

  4. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis

    PubMed Central

    Chen, Xin; He, Wan-ting; Hu, Lichen; Li, Jingxian; Fang, Yuan; Wang, Xin; Xu, Xiaozheng; Wang, Zhuo; Huang, Kai; Han, Jiahuai

    2016-01-01

    Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis. PMID:27573174

  5. A Quasi-Experimental Analysis of the Association between Family Income and Offspring Conduct Problems

    ERIC Educational Resources Information Center

    D'Onofrio, Brian M.; Goodnight, Jackson A.; Van Hulle, Carol A.; Rodgers, Joseph Lee; Rathouz, Paul J.; Waldman, Irwin D.; Lahey, Benjamin B.

    2009-01-01

    The study presents a quasi-experimental analysis of data on 9,194 offspring (ages 4-11 years old) of women from a nationally representative U.S. sample of households to test the causal hypotheses about the association between family income and childhood conduct problems (CPs). Comparison of unrelated individuals in the sample indicated a robust…

  6. Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.

    PubMed

    Vigouroux, Stéphane; Tabrizi, Reza; Melot, Cyril; Coiffard, Joelle; Lafarge, Xavier; Marit, Gérald; Bouabdallah, Krimo; Pigneux, Arnaud; Leguay, Thibaut; Dilhuydy, Marie-Sarah; Schmitt, Anna; Boiron, Jean-Michel; Milpied, Noël

    2011-01-01

    Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.

  7. Association of lipoprotein subclass distribution with use of selective and non-selective beta-blocker medications in patients with coronary heart disease.

    PubMed

    Superko, H R; Haskell, W L; Krauss, R M

    1993-06-01

    The relationship of beta-blocker drug use to plasma low density lipoprotein-cholesterol (LDL-C), lipoprotein mass distribution, (LDL, Sf0-12), intermediate density lipoproteins (IDL, Sf12-20), very low density lipoproteins (VLDL, Sf20-400), and high density lipoproteins (HDL, F(1.2)0-9) were examined in 206 men with coronary heart disease. Thirty-three used non-selective (NSEL), 49 used selective (SEL), and were compared to 124 who used no beta-blockade (NoBB). No significant between group differences were seen for potentially confounding variables. LDL and IDL mass, total cholesterol and LDL-cholesterol were not significantly different between groups. HDL-C was significantly lower in both NSEL (P < 0.005) and SEL (P < 0.01). NSEL and SEL had significantly lower HDL mass (P < 0.005 and P < 0.005) and SEL (P < 0.01 and P = 0.06), and HDL3 mass (P < 0.01 and P < 0.05). VLDL mass was significantly higher (P < 0.02) only in NSEL. Small LDL (Sf0-7) was not significantly different between groups and large LDL (Sf7-12) was significantly lower in NSEL (P < 0.05) and SEL (P < 0.05). LDL peak Sf was significantly lower in both NSEL (P < 0.005) and SEL (P < 0.02) compared to NoBB. Despite the lack of differences in levels of LDL-cholesterol, beta-blocker use is associated with a significant difference in the distribution of larger, more buoyant to smaller, more dense LDL particles. Reduced HDL levels in subjects on beta-blockade therapy are associated with reductions in both HDL2 and HDL3 subclasses.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effect of selective and non-selective serotonin receptor activation on L-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats.

    PubMed

    Tronci, E; Fidalgo, C; Stancampiano, R; Carta, M

    2015-10-01

    Selective activation of 5-HT1 receptors has been shown to produce near to full suppression of L-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease; however, a reduction of the therapeutic effect of L-DOPA has been reported in several studies. Conversely, we recently found that increasing the serotonergic tone with chronic administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) can reduce LID in 6-OHDA-lesioned rats, without affecting L-DOPA efficacy. To directly compare the effects of selective versus non-selective serotonin receptor activation, here we first tested different acute doses of the 5-HT1A/1B receptor agonist eltoprazine and 5-HTP on LID in order to identify doses of the individual compounds showing similar anti-dyskinetic efficacy in L-DOPA-primed dyskinetic rats. About 50% reduction of LID was observed with 0.1 mg/kg and 24 mg/kg of eltoprazine and 5-HTP, respectively; we then compared the effect of the two drugs, individually and in combination, on L-DOPA-induced stepping test in L-DOPA-naïve parkinsonian animals and LID over three weeks of L-DOPA treatment. Results showed that eltoprazine induced significant worsening of L-DOPA-mediated performance in the stepping test, while 5-HTP did not. Interestingly, combination of 5-HTP with eltoprazine prevented the reduction in the forelimb use induced by eltoprazine. Moreover, 5-HTP and eltoprazine given individually showed similar efficacy also upon chronic treatment, and had additive effect in dampening the appearance of LID when given in combination. Finally, chronic administration of eltoprazine and/or 5-HTP did not affect striatal serotonin innervation, compared to l-DOPA alone, as measured by serotonin transporter expression.

  9. Design of non-selective refocusing pulses with phase-free rotation axis by gradient ascent pulse engineering algorithm in parallel transmission at 7 T

    NASA Astrophysics Data System (ADS)

    Massire, Aurélien; Cloos, Martijn A.; Vignaud, Alexandre; Le Bihan, Denis; Amadon, Alexis; Boulant, Nicolas

    2013-05-01

    At ultra-high magnetic field (⩾7 T), 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 7 T, 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.

  10. Effect of selective and non-selective serotonin receptor activation on L-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats.

    PubMed

    Tronci, E; Fidalgo, C; Stancampiano, R; Carta, M

    2015-10-01

    Selective activation of 5-HT1 receptors has been shown to produce near to full suppression of L-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease; however, a reduction of the therapeutic effect of L-DOPA has been reported in several studies. Conversely, we recently found that increasing the serotonergic tone with chronic administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) can reduce LID in 6-OHDA-lesioned rats, without affecting L-DOPA efficacy. To directly compare the effects of selective versus non-selective serotonin receptor activation, here we first tested different acute doses of the 5-HT1A/1B receptor agonist eltoprazine and 5-HTP on LID in order to identify doses of the individual compounds showing similar anti-dyskinetic efficacy in L-DOPA-primed dyskinetic rats. About 50% reduction of LID was observed with 0.1 mg/kg and 24 mg/kg of eltoprazine and 5-HTP, respectively; we then compared the effect of the two drugs, individually and in combination, on L-DOPA-induced stepping test in L-DOPA-naïve parkinsonian animals and LID over three weeks of L-DOPA treatment. Results showed that eltoprazine induced significant worsening of L-DOPA-mediated performance in the stepping test, while 5-HTP did not. Interestingly, combination of 5-HTP with eltoprazine prevented the reduction in the forelimb use induced by eltoprazine. Moreover, 5-HTP and eltoprazine given individually showed similar efficacy also upon chronic treatment, and had additive effect in dampening the appearance of LID when given in combination. Finally, chronic administration of eltoprazine and/or 5-HTP did not affect striatal serotonin innervation, compared to l-DOPA alone, as measured by serotonin transporter expression. PMID:26119238

  11. Ability of preoperative falls to predict postsurgical outcomes in non-selected patients undergoing elective surgery at an academic medical centre: protocol for a prospective cohort study

    PubMed Central

    Ben Abdallah, Arbi; McKinnon, Sherry L; Wildes, Troy S; Avidan, Michael S

    2016-01-01

    Introduction Falls are increasingly recognised for their ability to herald impending health decline. Despite the likely susceptibility of postsurgical patients to falls, a detailed description of postoperative falls in an unselected surgical population has never been performed. One study suggests that preoperative falls may forecast postoperative complications. However, a larger study with non-selected surgical patients and patient-centred outcomes is needed to provide the generalisability and justification necessary to implement preoperative falls assessment into routine clinical practice. The aims of this study are therefore twofold. First, we aim to describe the main features of postoperative falls in a population of unselected surgical patients. Second, we aim to test the hypothesis that a history of falls in the 6 months prior to surgery predicts postoperative falls, poor quality of life, functional dependence, complications and readmission. Methods and analysis To achieve these goals, we study adult patients who underwent elective surgery at our academic medical centre and were recruited to participate in a prospective, survey-based cohort study called Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) (NCT02032030). Patients who reported falling in the 6 months prior to surgery will be considered ‘exposed.’ The primary outcome of interest is postoperative falls within 30 days of surgery. Secondary outcomes include postoperative functional dependence, quality of life (both physical and mental), in-hospital complications and readmission. Regression models will permit controlling for important confounders. Ethics and dissemination The home institution's Institutional Review Board approved this study (IRB ID number 201505035). The authors will publish the findings, regardless of the results. PMID:27655260

  12. Sequential radiation of unrelated organisms: the gall fly Eurosta solidaginis and the tumbling flower beetle Mordellistena convicta.

    PubMed

    Abrahamson, W G; Blair, C P; Eubanks, M D; Morehead, S A

    2003-09-01

    Host shifts and the formation of insect-host races are likely common processes in the speciation of herbivorous insects. The interactions of goldenrods Solidago (Compositae), the gall fly Eurosta solidaginis (Diptera: Tephritidae) and the beetle Mordellistena convicta (Coleoptera: Mordellidae) provide behavioural, ecological and genetic evidence of host races that may represent incipient species forming via sympatric speciation. We summarize evidence for Eurosta host races and show that M. convicta has radiated from goldenrod stems to Eurosta galls to form host-part races and, having exploited the galler's host shift, has begun to differentiate into host races within galls. Thus, host-race formation has occurred in two interacting, but unrelated organisms representing two trophic levels, resulting in 'sequential radiation' (escalation of biodiversity up the trophic system). Distributions of host races and their behavioural isolating mechanisms suggest sympatric differentiation. Such differentiation suggests host-race formation and subsequent speciation may be an important source of biodiversity.

  13. Finding local structural similarities among families of unrelated protein structures: a generic non-linear alignment algorithm.

    PubMed

    Lehtonen, J V; Denessiouk, K; May, A C; Johnson, M S

    1999-02-15

    We have developed a generic tool for the automatic identification of regions of local structural similarity in unrelated proteins having different folds, as well as for defining more global similarities that result from homologous protein structures. The computer program GENFIT has evolved from the genetic algorithm-based three-dimensional protein structure comparison program GA_FIT. GENFIT, however, can locate and superimpose regions of local structural homology regardless of their position in a pair of structures, the fold topology, or the chain direction. Furthermore, it is possible to restrict the search to a volume centered about a region of interest (e.g., catalytic site, ligand-binding site) in two protein structures. We present a number of examples to illustrate the function of the program, which is a parallel processing implementation designed for distribution to multiple machines over a local network or to run on a single multiprocessor computer.

  14. Design of high-performing hybrid meta-heuristics for unrelated parallel machine scheduling with machine eligibility and precedence constraints

    NASA Astrophysics Data System (ADS)

    Afzalirad, Mojtaba; Rezaeian, Javad

    2016-04-01

    This study involves an unrelated parallel machine scheduling problem in which sequence-dependent set-up times, different release dates, machine eligibility and precedence constraints are considered to minimize total late works. A new mixed-integer programming model is presented and two efficient hybrid meta-heuristics, genetic algorithm and ant colony optimization, combined with the acceptance strategy of the simulated annealing algorithm (Metropolis acceptance rule), are proposed to solve this problem. Manifestly, the precedence constraints greatly increase the complexity of the scheduling problem to generate feasible solutions, especially in a parallel machine environment. In this research, a new corrective algorithm is proposed to obtain the feasibility in all stages of the algorithms. The performance of the proposed algorithms is evaluated in numerical examples. The results indicate that the suggested hybrid ant colony optimization statistically outperformed the proposed hybrid genetic algorithm in solving large-size test problems.

  15. Herpesvirus-6 encephalitis complicated by Wernicke-Korsakoff syndrome in a pediatric recipient of unrelated cord blood transplantation.

    PubMed

    Carvajal, E; Verdeguer, A; Fernández, J M; Cañete, A; Castel, V

    2001-12-01

    A 10-year-old girl with M2 acute myeloid leukemia underwent an unrelated cord blood transplantation in refractory first relapse. On day +13, after 48 hours with fever, she showed a measles-like rash, and on day +15, she began experiencing neurologic symptoms (headache, tremors, weakness, nystagmus, mild confusion, speaking, taste, and behavior disturbances, and focal seizures). She also had amnesia for recent events with disability to learn, mimicking Wernicke-Korsakoff syndrome. Computed tomography of the brain and cerebrospinal fluid (CSF) and electroencephalogram were nonspecific. We found human herpesvirus 6 (HHV-6) DNA in CSF and cytomegalovirus in bronchoalveolar lavage using polymerase chain reaction techniques. Treatment with ganciclovir and foscarnet was effective, with total resolution of symptoms.

  16. X-linked creatine transporter defect: a report on two unrelated boys with a severe clinical phenotype.

    PubMed

    Anselm, I A; Anselm, I M; Alkuraya, F S; Salomons, G S; Jakobs, C; Fulton, A B; Mazumdar, M; Rivkin, M; Frye, R; Poussaint, T Young; Marsden, D

    2006-02-01

    We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation, absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation and was discovered upon subsequent review of the MRS. Molecular studies showed large genomic deletions of a large part of the 3' end of the complete open reading frame of the SLC6A8 gene. This report emphasizes the importance of MRS in evaluating neurological symptoms, broadens the phenotypic spectrum of CRTR and adds knowledge about the pathogenesis of creatine depletion in the brain and retina.

  17. Longitudinal genetic analysis of internalizing and externalizing problem behavior in adopted biologically related and unrelated sibling pairs.

    PubMed

    Huizink, Anja C; van den Berg, Mijke P; van der Ende, Jan; Verhulst, Frank C

    2007-02-01

    To obtain a better understanding of how genetic and environmental processes are involved in the stability and change in problem behavior from early adolescence into adulthood, studies with genetically informative samples are important. The present study used parent-reported data on internalizing and externalizing problem behavior of adoptees at mean ages 12.4, 15.5 and 26.3. In this adoption study adopted biologically related sibling pairs shared on average 50% of their genes and were brought up in the same family environment, whereas adopted biologically unrelated sibling pairs only shared their family environment. The resemblance between these adopted biologically related (N = 106) and unrelated sibling pairs (N=230) was compared and examined over time. We aimed to investigate (1) to what extent are internalizing and externalizing problem behavior stable from early adolescence into adulthood, and (2) whether the same or different genetic and environmental factors affect these problem behaviors at the 3 assessments. Our results show that both internalizing (rs ranging from .34 to .58) and externalizing behavior (rs ranging from .47 to .69) were rather stable over time. For internalizing and externalizing problem behavior it was found that both genetic and shared environmental influences could be modeled by an underlying common factor, which explained variance in problem behavior from early adolescence into adulthood and accounted for stability over time. The nonshared environmental influences were best modeled by a Cholesky decomposition for internalizing behavior, whereas a time-specific influence of the nonshared environment was included in the final model of externalizing behavior.

  18. Higher plasma orexin A levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls.

    PubMed

    Manzardo, Ann M; Johnson, Lisa; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

    2016-08-01

    Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia, and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc. PMID:27214028

  19. Higher plasma orexin a levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls.

    PubMed

    Manzardo, Ann M; Johnson, Lisa; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

    2016-09-01

    Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat, and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1,028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc. PMID:27518917

  20. High proportion of large genomic deletions and a genotype–phenotype update in 80 unrelated families with juvenile polyposis syndrome

    PubMed Central

    Aretz, S; Stienen, D; Uhlhaas, S; Stolte, M; Entius, M M; Loff, S; Back, W; Kaufmann, A; Keller, K‐M; Blaas, S H; Siebert, R; Vogt, S; Spranger, S; Holinski‐Feder, E; Sunde, L; Propping, P; Friedl, W

    2007-01-01

    Background In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. Methods Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. Results By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). Conclusions Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype‐phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted. PMID:17873119

  1. Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B cells with a homologous repertoire in unrelated individuals

    PubMed Central

    Patil, Sarita U.; Ogunniyi, Adebola O.; Calatroni, Agustin; Tadigotla, Vasisht R.; Ruiter, Bert; Ma, Alex; Moon, James; Love, J.Christopher; Shreffler, Wayne G.

    2015-01-01

    Background Peanut oral immunotherapy (PNOIT) induces persistent tolerance to peanut in a subset of patients and induces specific antibodies which may play a role in clinical protection. The contribution of induced antibody clones to clinical tolerance in PNOIT is unknown, however. Objective We hypothesized that PNOIT induces a clonal, allergen-specific B cell response, which could serve as a surrogate for clinical outcomes. Methods We used a fluorescent Ara h 2 multimer for affinity-selection of Ara h 2-specific B cells, and subsequent single cell immunoglobulin amplification. Diversity of related clones was evaluated by next-generation sequencing (NGS) of immunoglobulin heavy chains from circulating memory B cells using 2×250 paired-end sequencing on the Illumina MiSeq platform. Results Expression of class-switched antibodies from Ara h 2 positive cells confirms enrichment for Ara h 2 specificity. PNOIT induces an early and transient expansion of circulating Ara h 2 specific memory B cells that peaks at week 7. Ara h 2-specific sequences from memory cells have rates of non-silent mutations consistent with affinity maturation. The repertoire of Ara h 2-specific antibodies is oligoclonal. NGS-based repertoire analysis of circulating memory B cells, reveals evidence for convergent selection of related sequences in 3 unrelated subjects, suggesting the presence of similar Ara h 2-specific B cell clones. Conclusions Using a novel affinity selection approach to identify antigen-specific B cells, we demonstrate that the early PNOIT induced Ara h 2-specific BCR repertoire is oligoclonal, somatically hypermutated and shares similar clonal groups among unrelated individuals consistent with convergent selection. PMID:25985925

  2. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia

    PubMed Central

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-01-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16–72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15–2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  3. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia.

    PubMed

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-05-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16-72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15-2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  4. Effect of major histocompatibility complex haplotype matching by C4 and MICA genotyping on acute graft versus host disease in unrelated hematopoietic stem cell transplantation.

    PubMed

    Park, Yongjung; Cheong, June-Won; Park, Myoung Hee; Kim, Myoung Soo; Kim, Jong Sun; Kim, Hyon-Suk

    2016-02-01

    We explored whether matching of human leukocyte antigen (HLA) haplotypes between the recipient and donor of hematopoietic stem cell transplantation (HSCT) predicted by C4 and MICA typing is associated with the incidence of acute graft versus host disease (aGVHD). DNA preparations collected from a total of 81 recipient and donor pairs were used for PCR-based C4 subtyping and/or MICA sequence-based typing. Incidences of aGVHD were compared according to C4 and MICA matching. The six most common MICA alleles were MICA*008:01, *010:01, *002:01, *004, *009:01/049, and *012:01. Among the 59 unrelated pairs, HLA alleles were matched in 34 (57.6%). C4 subtypes were identical between the recipient and donor in 28 (82.4%) HLA-matched unrelated pairs, while MICA genotypes were matched in all HLA-matched unrelated pairs. In the 22 HLA-matched related pairs, all recipients showed identical C4 subtypes with their respective donors. In multivariate analysis, C4 mismatch was a significant risk factor associated with the development of aGVHD in unrelated HSCT (hazard ratio=3.24, P=0.006). PCR-based C4 subtyping is a simple method for assessing the genetic identity of the HLA region between a recipient and unrelated donor. This test would be also useful for prediction of aGVHD in HSCT.

  5. The non-selective cannabinoid receptor agonist WIN 55,212-2 attenuates responses of C-fiber nociceptors in a murine model of cancer pain

    PubMed Central

    Uhelski, Megan L.; Cain, David M.; Harding-Rose, Catherine; Simone, Donald A.

    2013-01-01

    Pain from cancer can be severe, difficult to treat, and greatly diminishes patients’ quality of life. It is therefore important to gain new information on the mechanisms of cancer pain and develop new treatment strategies. We have used a murine model of bone cancer pain to investigate underlying peripheral neural mechanisms and novel treatment approaches. In this model, implantation of fibrosarcoma cells into and around the calcaneous bone produces mechanical and thermal hyperalgesia in mice. C-fiber nociceptors in tumor-bearing mice develop spontaneous ongoing activity and sensitization to thermal stimuli. However, it is unclear whether sensitization of nociceptors to mechanical stimuli underlies the mechanical hyperalgesia seen in tumor-bearing mice. We therefore examined responses of C-fiber nociceptors to suprathreshold mechanical stimuli in tumor-bearing mice and found they did not differ from those of C-nociceptors in control mice. Thus, sensitization of C-fiber nociceptors to mechanical stimulation does not appear to underlie tumor-evoked mechanical hyperalgesia in this murine model of bone cancer pain. We also examined the effect of the non-selective cannabinoid receptor agonist, WIN 55, 212-2, on spontaneous activity and responses evoked by mechanical stimuli of C-fiber nociceptors innervating the tumor-bearing paw. Selective CB1 and CB2 antagonists were administered to determine the contribution of each receptor subtype to the effects of WIN 55,212-2. Intraplantar administration of WIN 55,212-2 attenuated spontaneous discharge and responses evoked by mechanical stimulation of C-fiber nociceptors. These effects were inhibited by prior intraplantar administration of selective CB1 (AM281) or CB2 (AM630) receptor antagonists but not by vehicle. These results indicate that activation of either CB1 or CB2 receptors reduced the spontaneous activity of C-fiber nociceptors associated with tumor growth as well as their evoked responses. Our results provide

  6. Non-selective cyclooxygenase inhibition before periodic acceleration (pGz) cardiopulmonary resuscitation (CPR) in a porcine model of ventricular fibrillation.

    PubMed

    Bassuk, Jorge A; Wu, Dongmei; Lozano, Hector; Arias, Jaqueline; Kurlansky, Paul; Lamas, Gervasio A; Adams, Jose A

    2008-05-01

    Whole body periodic acceleration (pGz) along the spinal axis is a novel method of cardiopulmonary resuscitation (CPR). Oscillatory motion of the supine body in a horizontal fashion provides ventilation and blood flow to vital organs during cardiac arrest and pulsatile shear stress to the vascular endothelium. We previously showed in pigs that pGz-CPR affords better overall survival, post resuscitation myocardial function, and neurological outcomes compared to conventional chest compression CPR. pGz through pulsatile shear stress on the vascular endothelium elicits acute production of prostaglandins and endothelial-derived nitric oxide (eNO) in whole animal models and in vitro preparations. The salutary effects associated with pGz-CPR compared to chest compression CPR are in part related to endothelial-derived nitric oxide. Both eNO and prostaglandins are cardioprotective in ischemia reperfusion models. To differentiate between the roles of these mediators, indomethacin a non-selective cyclooxygenase inhibitor (COX) was used as a tool to investigate prostaglandin effects during pGz-CPR by acute outcomes of survival, cardioprotection and regional blood flows (RBF). Two groups of anesthetized, intubated pigs weighing 25-36kg were studied. Prior to electrical induction of ventricular fibrillation (VF) animals received equal volumes of either saline placebo Control (CONT) (n=9) or indomethacin (INDO), (n=8), (2mg/kg). After 3min of unsupported VF, both groups received 15min of pGz-CPR followed by pharmacologic and electrical attempts for resuscitation. Return of circulation (ROSC) to 3h occurred in (78%) in CONT and (63%) in INDO pretreated animals. There was no statistically significant difference in hemodynamics between groups at baseline or during the protocol. At baseline, INDO caused a decrease in brain RBF. Two hours after ROSC, INDO blunted the hyperemia response to brain and heart. Echocardiographic evidence of myocardial dysfunction was most notable for the

  7. In the polymorphic ciliate Tetrahymena vorax, the non-selective phagocytosis seen in microstomes changes to a highly selective process in macrostomes.

    PubMed

    Grønlien, Heidi K; Berg, Trond; Løvlie, Arne M

    2002-07-01

    Ciliates use phagocytosis to acquire edible particles. The polymorphic ciliate Tetrahymena vorax appears in two forms ('microstomes' and 'macrostomes'). Transformation of microstomes into macrostomes takes place in the presence of the ciliate Tetrahymena thermophila and enables the macrostome to phagocytose the latter species. The non-specific, constitutive phagocytosis in microstomes thereby changes into a specific inducible process in macrostomes. The purpose of this study was to determine whether the phagocytotic process in macrostomes is specifically aimed at catching T. thermophila. The two forms of phagocytosis represent an interesting model system for studying the mechanism whereby phagosomes are formed. The macrostomal form capture deciliated and ciliated Tetrahymena thermophila, latex beads with diameters of 20.3 and 30.0 microm and small microstomal cells. However, the macrostomes select T. thermophila as a prey when they have the opportunity to choose between deciliated T. thermophila and latex beads and between T. thermophila and microstomes. The non-selective formation of phagosomes seen in microstomes changes to a highly selective process during the transformation to macrostomes. Unlike microstomes, macrostomes do not form a closed vacuole after capturing a latex bead, indicating that mechanical stimulation by the prey does not in itself trigger phagocytosis in the macrostomal form of T. vorax. Although macrostomes captured T. thermophila in preference to microstomes, phagocytosis of microstomes started immediately following capture, indicating that the substance/molecule that triggers the formation of the phagosome is not specific for T. thermophila cells. After capturing a T. thermophila cell, the macrostomal cell, which normally swims in a forward direction, reverses direction and swims backwards for a short time before starting to rotate. Macrostomal cells did not change their swimming pattern after capturing a latex bead. We believe, therefore

  8. Differential effects of selective frankincense (Ru Xiang) essential oil versus non-selective sandalwood (Tan Xiang) essential oil on cultured bladder cancer cells: a microarray and bioinformatics study

    PubMed Central

    2014-01-01

    cancer cell death. While frankincense essential oil elicited selective cancer cell death via NRF-2-mediated oxidative stress, sandalwood essential oil induced non-selective cell death via DNA damage and cell cycle arrest. PMID:25006348

  9. Characterization of the B*5002-Cw*0602-DRB1*0406-DQB1*0402 Haplotype: impact on the unrelated-bone marrow donor search strategy.

    PubMed

    Ansart-Pirenne, H; Dufossé, F; Duval, M; Cracco, P; Jambou, M; Pédron, B; Vilmer, E; Sterkers, G

    2001-02-01

    Improvements in HLA-typing by DNA-based methods now allow accurate genotyping of unrelated bone marrow (UBM) donors and recipients and also definition of haplotypes. In this regard, B*5002 has been predicted in linkage disequilibrium with Cw*0602, DRB1*0406 and DQB1*0402 based on the frequency of allele coexistence. Here, we confirm this assumption by HLA genotyping of four informative families and three unrelated individuals. In the four families, the extended haplotype HLA-B*5002, -Cw*0602, -DRB1*0406, DQB1*0402 can be definitely assigned by the mode of heritance. Furthermore, this association of alleles was also found in the three B*5002 unrelated individuals. Knowledge of the frequent linkage disequilibrium of these rare alleles can improve UBM donor search strategies.

  10. The Contagion of Interstate Violence: Reminders of Historical Interstate (but Not Intrastate) Violence Increase Support for Future Violence Against Unrelated Third-Party States.

    PubMed

    Li, Mengyao; Leidner, Bernhard; Euh, Hyun; Choi, Hoon-Seok

    2016-08-01

    Five experiments investigated the war contagion phenomenon in the context of international relations, hypothesizing that reminders of past inter- (but not intra-) state war will increase support for future, unrelated interstate violence. After being reminded of the Korean War as an interstate rather than intrastate conflict, South Koreans showed stronger support for violent responses to new, unrelated interstate tensions (Study 1). Replicating this war contagion effect among Americans, we demonstrated that it was mediated by heightened perceived threat from, and negative images of, a fictitious country unrelated to the past war (Study 2), and moderated by national glorification (Study 3). Study 4, using another international conflict in the U.S. history, provided further conceptual replication. Finally, Study 5 included a baseline in addition to the inter- versus intrastate manipulation, yielding further support for the generalized effect of past interstate war reminders on preferences for aggressive approaches to new interstate tensions. PMID:27257097

  11. Octopamine and cooperation: octopamine regulates the disappearance of cooperative behaviours between genetically unrelated founding queens in the ant

    PubMed Central

    Koyama, Satoshi; Matsui, Shingo; Satoh, Toshiyuki; Sasaki, Ken

    2015-01-01

    We investigated whether octopamine (OA) is associated with the disappearance of cooperation in Polyrhachis moesta ant queens. Queens of P. moesta facultatively found the colony with genetically unrelated queens. The founding queens perform frequent food exchange with these non-related queens and partake in cooperative brood rearing, whereas single colony queens exclude non-related queens via aggressive behaviour. Thus, aggression is a factor that reduces cooperation. Given that aggression is generally associated with brain OA in insects, we hypothesized that OA controls the behavioural change in cooperation in the ant queen, via an increase in aggression. To test this hypothesis, we compared the amounts of OA and related substances in the brain between founding and colony queens, and observed the interaction of founding queens following oral OA administration. The brain OA levels in colony queens were significantly higher than those in founding queens. Oral administration of OA to founding queens caused significantly less trophallaxis and allogrooming behaviour than in the control founding queens, but with no significant increase in aggression. These results suggest that OA promotes the disappearance of cooperation in founding queens of P. moesta. This is the first study to reveal the neuroendocrine mechanism of cooperation in ant queens. PMID:26085498

  12. Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids

    NASA Astrophysics Data System (ADS)

    Niu, Jia; Hili, Ryan; Liu, David R.

    2013-04-01

    The translation of DNA sequences into corresponding biopolymers enables the production, function and evolution of the macromolecules of life. In contrast, methods to generate sequence-defined synthetic polymers with similar levels of control have remained elusive. Here, we report the development of a DNA-templated translation system that enables the enzyme-free translation of DNA templates into sequence-defined synthetic polymers that have no necessary structural relationship with nucleic acids. We demonstrate the efficiency, sequence-specificity and generality of this translation system by oligomerizing building blocks including polyethylene glycol, α-(D)-peptides, and β-peptides in a DNA-programmed manner. Sequence-defined synthetic polymers with molecular weights of 26 kDa containing 16 consecutively coupled building blocks and 90 densely functionalized β-amino acid residues were translated from DNA templates using this strategy. We integrated the DNA-templated translation system developed here into a complete cycle of translation, coding sequence replication, template regeneration and re-translation suitable for the iterated in vitro selection of functional sequence-defined synthetic polymers unrelated in structure to nucleic acids.

  13. Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors.

    PubMed

    Shaw, Peter J; Kan, Fangyu; Woo Ahn, Kwang; Spellman, Stephen R; Aljurf, Mahmoud; Ayas, Mouhab; Burke, Michael; Cairo, Mitchell S; Chen, Allen R; Davies, Stella M; Frangoul, Haydar; Gajewski, James; Gale, Robert Peter; Godder, Kamar; Hale, Gregory A; Heemskerk, Martin B A; Horan, John; Kamani, Naynesh; Kasow, Kimberly A; Chan, Ka Wah; Lee, Stephanie J; Leung, Wing H; Lewis, Victor A; Miklos, David; Oudshoorn, Machteld; Petersdorf, Effie W; Ringdén, Olle; Sanders, Jean; Schultz, Kirk R; Seber, Adriana; Setterholm, Michelle; Wall, Donna A; Yu, Lolie; Pulsipher, Michael A

    2010-11-11

    Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.

  14. Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency.

    PubMed

    John, Tami; Walter, Jolan E; Schuetz, Catherina; Chen, Karin; Abraham, Roshini S; Bonfim, Carmem; Boyce, Thomas G; Joshi, Avni Y; Kang, Elizabeth; Carvalho, Beatriz Tavares Costa; Mahajerin, Arash; Nugent, Diane; Puthenveetil, Geetha; Soni, Amit; Su, Helen; Cowan, Morton J; Notarangelo, Luigi; Buchbinder, David

    2016-10-01

    The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency. PMID:27539235

  15. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation

    PubMed Central

    Ciurea, Stefan O.; Thall, Peter F.; Wang, Xuemei; Wang, Sa A.; Hu, Ying; Cano, Pedro; Aung, Fleur; Rondon, Gabriela; Molldrem, Jeffrey J.; Korbling, Martin; Shpall, Elizabeth J.; de Lima, Marcos; Champlin, Richard E.

    2011-01-01

    Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft failure in mismatched hematopoietic stem cell transplantation; however, their role in the development of graft failure in matched unrelated donor (MUD) transplantation remains unclear. We hypothesize that DSAs against a mismatched HLA-DPB1 locus is associated with graft failure in this setting. The presence of anti-HLA Abs before transplantation was determined prospectively in 592 MUD transplantation recipients using mixed-screen beads in a solid-phase fluorescent assay. DSA identification was performed using single-Ag beads containing the corresponding donor's HLA-mismatched Ags. Anti-HLA Abs were detected in 116 patients (19.6%), including 20 patients (3.4%) with anti-DPB1 Abs. Overall, graft failure occurred in 19 of 592 patients (3.2%), including 16 of 584 (2.7%) patients without anti-HLA Abs compared with 3 of 8 (37.5%) patients with DSA (P = .0014). In multivariate analysis, DSAs were the only factor highly associated with graft failure (P = .0001; odds ratio = 21.3). Anti-HLA allosensitization was higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in women with 1 (P = .008) and 2 or more pregnancies (P = .0003) than in men. We conclude that the presence of anti-DPB1 DSAs is associated with graft failure in MUD hematopoietic stem cell transplantation. PMID:21967975

  16. Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency.

    PubMed

    John, Tami; Walter, Jolan E; Schuetz, Catherina; Chen, Karin; Abraham, Roshini S; Bonfim, Carmem; Boyce, Thomas G; Joshi, Avni Y; Kang, Elizabeth; Carvalho, Beatriz Tavares Costa; Mahajerin, Arash; Nugent, Diane; Puthenveetil, Geetha; Soni, Amit; Su, Helen; Cowan, Morton J; Notarangelo, Luigi; Buchbinder, David

    2016-10-01

    The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.

  17. Donor KIR B Genotype Improves Progression Free Survival of Non-Hodgkin lymphoma Patients Receiving Unrelated Donor Transplantation

    PubMed Central

    Bachanova, Veronika; Weisdorf, Daniel J.; Wang, Tao; Marsh, Steven G.E.; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R.; Ladner, Martha; Guethlein, Lisbeth A.; Parham, Peter; Miller, Jeffrey S.; Cooley, Sarah A.

    2016-01-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes associate with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T-cell replete marrow or peripheral blood grafts. Sixty four percent (n=396) of donor-recipient pairs were 10/10 allele HLA-matched; 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; CI 21–32% vs. 37%; CI 27–46%, p=0.05) compared with KIR A/A donors, resulting in improved 5 year progression-free survival (PFS) (35%; CI 26–44% vs. 22%; CI 11–35%; p=0.007). In multivariate analysis, use of KIR B/x donors associated with significantly reduced relapse risk (RR 0.63, p=0.02) and improved PFS (RR 0.71, p=0.008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplants, and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. PMID:27220262

  18. Abnormal expansion of naïve B lymphocytes after unrelated cord blood transplantation – a case report

    PubMed Central

    SHONO, Y; TOUBAI, T; OTA, S; IBATA, M; MASHIKO, S; HIRATE, D; MIURA, Y; UMEHARA, S; TOYOSHIMA, N; TANAKA, J; ASAKA, M; IMAMURA, M

    2006-01-01

    A 33-year-old woman underwent unrelated cord blood transplantation (U-CBT) for myelodysplastic syndrome (MDS)-related secondary AML. She showed impressive increases in the number of CD19+ B cells in bone marrow and CD19+27−IgD+ B cells in peripheral blood from about 1 month to 3 months after U-CBT. The serum level of IL-6 temporarily increased after transplantation, and this increase seemed to be correlated with the expansion of CD19+ B cells. Although, compared with BMT, little is known about the kinetics of hematological and immunological reconstitution in U-CBT, there was initial B-cell recovery after CBT as some described. This B cell recovery may be associated with a high number of B-cell precursors present in cord blood (CB). The phenomenon of naïve B lymphocyte expansion that we found might be associated with a high number of B-cell precursors present in CB. PMID:16999729

  19. Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.

    PubMed

    Millat, G; Chevalier, P; Restier-Miron, L; Da Costa, A; Bouvagnet, P; Kugener, B; Fayol, L; Gonzàlez Armengod, C; Oddou, B; Chanavat, V; Froidefond, E; Perraudin, R; Rousson, R; Rodriguez-Lafrasse, C

    2006-09-01

    Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes. PMID:16922724

  20. Overlapping submicroscopic deletions in Xq28 in two unrelated boys with developmental disorders: Identification of a gene near FRAXE

    SciTech Connect

    Gedeon, A.K.; Sutherland, G.R. |; Ades, L.C.; Gecz, J.; Baker, E.; Mulley, J.C.; Keinaenen, M.; Kaeaeriaeinen, H.

    1995-04-01

    Two unrelated boys are described with delay in development and submicroscopic deletions in Xq28, near FRAXE. Molecular diagnosis to exclude the fragile X (FRAXA) syndrome used the direct probe pfxa3, together with a control probe pS8 (DXS296), against PstI restriction digests of DNA. Deletions were detected initially by the control probe pS8, which is an anonymous fragment subcloned from YAC 539, within 1 Mb distal to FRAXA. Further molecular analyses determined that the maximum size of the deletion is <100 kb in one boy (MK) and is wholly overlapped by the deletion of up to {approximately}200 kb in the other (CB). These deletions lie between the sequences detected by the probe VK21C (DXS296) and a dinucleotide repeat VK18AC (DXS295). The patient MK had only speech delay with otherwise normal development, while patient CB had global developmental delay that included speech delay. Detection of overlapping deletions in these two cases led to speculation that coding sequences of a gene(s) important in language development may be affected. Hybridization of the pS8 and VK21A probes to zooblots revealed cross-species homology. This conservation during evolution suggested that this region contains sequences with functional significance in normal development. The VK21A probe detected a 9.5-kb transcript in placenta and brain and a smaller, 2.5-kb, transcript in other tissues analyzed. 26 refs., 6 figs.

  1. Octopamine and cooperation: octopamine regulates the disappearance of cooperative behaviours between genetically unrelated founding queens in the ant.

    PubMed

    Koyama, Satoshi; Matsui, Shingo; Satoh, Toshiyuki; Sasaki, Ken

    2015-06-01

    We investigated whether octopamine (OA) is associated with the disappearance of cooperation in Polyrhachis moesta ant queens. Queens of P. moesta facultatively found the colony with genetically unrelated queens. The founding queens perform frequent food exchange with these non-related queens and partake in cooperative brood rearing, whereas single colony queens exclude non-related queens via aggressive behaviour. Thus, aggression is a factor that reduces cooperation. Given that aggression is generally associated with brain OA in insects, we hypothesized that OA controls the behavioural change in cooperation in the ant queen, via an increase in aggression. To test this hypothesis, we compared the amounts of OA and related substances in the brain between founding and colony queens, and observed the interaction of founding queens following oral OA administration. The brain OA levels in colony queens were significantly higher than those in founding queens. Oral administration of OA to founding queens caused significantly less trophallaxis and allogrooming behaviour than in the control founding queens, but with no significant increase in aggression. These results suggest that OA promotes the disappearance of cooperation in founding queens of P. moesta. This is the first study to reveal the neuroendocrine mechanism of cooperation in ant queens. PMID:26085498

  2. Phenotypic expressions of a Gly154Arg mutation in type II collagen in two unrelated patients with spondyloepimetaphyseal dysplasia (SEMD)

    SciTech Connect

    Kaitila, I.; Marttinen, E.; Koerkkoe, J.; Ala-Kokko, L.

    1996-05-03

    Type II collagenopathies consist of chondrodysplasia ranging from lethal to mild in severity. A large number of mutations has been found in the COL2A1 gene. Glycine substitutions have been the most common types of mutation. Genotype-phenotype correlations in type II collagenopathies have not been established, partly because of insufficient clinical and radiographic description of the patients. We found a glycine-to-arginine substitution at position 154 in type II collagen in two unrelated isolated propositi with spondyloepimetaphyseal dysplasia and provide a comparative clinical and radiographic analysis from birth to young adulthood for this condition. The clinical phenotype was disproportionate short stature with varus/valgus deformities of the lower limbs requiring corrective osteotomies, and lumbar lordosis. The skeletal radiographs showed an evolution from short tubular bones, delayed epiphyseal development, and mild vertebral involvement to severe metaphyseal dysplasia with dappling irregularities, and hip {open_quotes}dysplasia.{close_quotes} The metaphyseal abnormalities disappeared by adulthood. 27 refs., 11 figs., 1 tab.

  3. Characterization of unrelated strains of Staphylococcus schleiferi by using ribosomal DNA fingerprinting, DNA restriction patterns, and plasmid profiles.

    PubMed Central

    Grattard, F; Etienne, J; Pozzetto, B; Tardy, F; Gaudin, O G; Fleurette, J

    1993-01-01

    The molecular characteristics of 31 unrelated strains of Staphylococcus schleiferi isolated from 13 hospitals between 1973 and 1991 were determined by ribosomal DNA fingerprinting by using a digoxigenin-labeled DNA probe, genomic DNA restriction patterns, and plasmid profiles. Only six strains harbored one or two plasmids. DNA restriction analysis, which was carried out with five endonucleases (EcoRI, HindIII, PstI, PvuII, and ClaI), did not allow us to discriminate between isolates. Ribotyping with HindIII, ClaI, or EcoRI enzymes generated six, seven, and nine distinct patterns, respectively. With the combination ClaI-EcoRI, 13 ribotypes were obtained among the 31 strains, suggesting a relative heterogeneity within the species. Moreover, all strains shared two or three common bands, according to the endonuclease used, which were relatively specific for S. schleiferi in comparison with the ribosomal banding patterns described for other coagulase-negative staphylococci. These results illustrate that ribotyping can be used for the epidemiological investigation of S. schleiferi isolates and possibly for taxonomic analysis in this species. Images PMID:8385149

  4. Poster — Thur Eve — 41: Considerations for Patients with Permanently Implant Radioactive Sources Requiring Unrelated Surgery

    SciTech Connect

    Basran, P. S; Beckham, WA; Baxter, P

    2014-08-15

    Permanent implant of sealed radioactive sources is an effective technique for treating cancer. Typically, the radioactive sources are implanted in and near the disease, depositing dose locally over several months. There may be instances where these patients must undergo unrelated surgical procedures when the radioactive material remains active enough to pose risks. This work explores these risks, discusses strategies to mitigate those risks, and describes a case study for a permanent I-125 prostate brachytherapy implant patient who developed colo-rectal cancer and required surgery 6 months after brachytherapy. The first consideration is identifying the risk from unwarranted radiation to the patient and staff before, during, and after the surgical procedure. The second is identifying the risk the surgical procedure may have on the efficacy of the brachytherapy implant. Finally, there are considerations for controlling for radioactive substances from a regulatory perspective. After these risks are defined, strategies to mitigate those risks are considered. These strategies may include applying the concepts of ALARA, the use of protective equipment and developing a best practice strategy with the operating room team. We summarize this experience with some guidelines: If the surgical procedure is near (ex: 5 cm) of the implant; and, the surgical intervention may dislodge radioisotopes enough to compromise treatment or introduces radiation safety risks; and, the radioisotope has not sufficiently decayed to background levels; and, the surgery cannot be postponed, then a detailed analysis of risk is advised.

  5. Synonymous Codon Usage Bias in the Plastid Genome is Unrelated to Gene Structure and Shows Evolutionary Heterogeneity.

    PubMed

    Qi, Yueying; Xu, Wenjing; Xing, Tian; Zhao, Mingming; Li, Nana; Yan, Li; Xia, Guangmin; Wang, Mengcheng

    2015-01-01

    Synonymous codon usage bias (SCUB) is the nonuniform usage of codons, occurring often in nearly all organisms. Our previous study found that SCUB is correlated with intron number, is unequal among exons in the plant nuclear genome, and mirrors evolutionary specialization. However, whether this rule exists in the plastid genome has not been addressed. Here, we present an analysis of SCUB in the plastid genomes of 25 species from lower to higher plants (algae, bryophytes, pteridophytes, gymnosperms, and spermatophytes). We found NNA and NNT (A- and T-ending codons) are preferential in the plastid genomes of all plants. Interestingly, this preference is heterogeneous among taxonomies of plants, with the strongest preference in bryophytes and the weakest in pteridophytes, suggesting an association between SCUB and plant evolution. In addition, SCUB frequencies are consistent among genes with varied introns and among exons, indicating that the bias of NNA and NNT is unrelated to either intron number or exon position. Further, SCUB is associated with DNA methylation-induced conversion of cytosine to thymine in the vascular plants but not in algae or bryophytes. These data demonstrate that these SCUB profiles in the plastid genome are distinctly different compared with the nuclear genome.

  6. The Stability and Formation of Native Proteins from Unfolded Monomers Is Increased through Interactions with Unrelated Proteins

    PubMed Central

    Rodríguez-Almazán, Claudia; Torner, Francisco J.; Costas, Miguel; Pérez-Montfort, Ruy; de Gómez-Puyou, Marieta Tuena; Puyou, Armando Gómez

    2007-01-01

    The intracellular concentration of protein may be as high as 400 mg per ml; thus it seems inevitable that within the cell, numerous protein-protein contacts are constantly occurring. A basic biochemical principle states that the equilibrium of an association reaction can be shifted by ligand binding. This indicates that if within the cell many protein-protein interactions are indeed taking place, some fundamental characteristics of proteins would necessarily differ from those observed in traditional biochemical systems. Accordingly, we measured the effect of eight different proteins on the formation of homodimeric triosephosphate isomerase from Trypanosoma brucei (TbTIM) from guanidinium chloride unfolded monomers. The eight proteins at concentrations of micrograms per ml induced an important increase on active dimer formation. Studies on the mechanism of this phenomenon showed that the proteins stabilize the dimeric structure of TbTIM, and that this is the driving force that promotes the formation of active dimers. Similar data were obtained with TIM from three other species. The heat changes that occur when TbTIM is mixed with lysozyme were determined by isothermal titration calorimetry; the results provided direct evidence of the weak interaction between apparently unrelated proteins. The data, therefore, are strongly suggestive that the numerous protein-protein interactions that occur in the intracellular space are an additional control factor in the formation and stability of proteins. PMID:17551578

  7. 4-hydroxyphenylpyruvate dioxygenase catalysis: identification of catalytic residues and production of a hydroxylated intermediate shared with a structurally unrelated enzyme.

    PubMed

    Raspail, Corinne; Graindorge, Matthieu; Moreau, Yohann; Crouzy, Serge; Lefèbvre, Bertrand; Robin, Adeline Y; Dumas, Renaud; Matringe, Michel

    2011-07-22

    4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the conversion of 4-hydroxyphenylpyruvate (HPP) into homogentisate. HPPD is the molecular target of very effective synthetic herbicides. HPPD inhibitors may also be useful in treating life-threatening tyrosinemia type I and are currently in trials for treatment of Parkinson disease. The reaction mechanism of this key enzyme in both plants and animals has not yet been fully elucidated. In this study, using site-directed mutagenesis supported by quantum mechanical/molecular mechanical theoretical calculations, we investigated the role of catalytic residues potentially interacting with the substrate/intermediates. These results highlight the following: (i) the central role of Gln-272, Gln-286, and Gln-358 in HPP binding and the first nucleophilic attack; (ii) the important movement of the aromatic ring of HPP during the reaction, and (iii) the key role played by Asn-261 and Ser-246 in C1 hydroxylation and the final ortho-rearrangement steps (numbering according to the Arabidopsis HPPD crystal structure 1SQD). Furthermore, this study reveals that the last step of the catalytic reaction, the 1,2 shift of the acetate side chain, which was believed to be unique to the HPPD activity, is also catalyzed by a structurally unrelated enzyme.

  8. Impact of marrow unrelated donor search duration on outcome of children with acute lymphoblastic leukemia in second remission.

    PubMed

    Dini, G; Valsecchi, M Grazia; Micalizzi, C; Busca, A; Balduzzi, A; Arcese, W; Cesaro, S; Prete, A; Rabusin, M; Mazzolari, E; Di Bartolomeo, P; Sacchi, N; Pession, A; Giorgiani, G; Lanino, E; Lamparelli, T; Favre, C; Bosi, A; Manzitti, C; Galimberti, S; Locatelli, F

    2003-08-01

    We analyzed the outcome of 167 consecutive children with second CR acute lymphoblastic leukemia (ALL), for whom an unrelated donor (UD) search was activated between 1989 and 1998 at a median time of 2 months after relapse. A suitable donor was identified for 70 patients at 1 year and 6.5 months before and after 1995 from search activation, respectively; a further leukemia relapse occurred during the search in 94 children at a median of 4 months after search activation, 36 of whom underwent UD (14) or other types of transplant (22), beyond second CR, while 58 died of progressive disease. Of 73 patients not experiencing a second relapse, 64 underwent UD (46) or other types of transplant (18), while nine proceeded with chemotherapy, and only four of them survived. The 3-year disease-free survival (DFS) from second CR for the 167 patients is 15.1%, whereas 3-year DFS after transplant for the 60 UD and 40 alternative donor transplanted children is 31.6 and 25.4%, respectively. In conclusion, a further relapse is the main factor adversely affecting outcome of children with second CR ALL. Thus, for these patients, the search should be activated early after relapse and either a UD or an alternative transplant should be performed as early as possible.

  9. Synonymous Codon Usage Bias in the Plastid Genome is Unrelated to Gene Structure and Shows Evolutionary Heterogeneity

    PubMed Central

    Qi, Yueying; Xu, Wenjing; Xing, Tian; Zhao, Mingming; Li, Nana; Yan, Li; Xia, Guangmin; Wang, Mengcheng

    2015-01-01

    Synonymous codon usage bias (SCUB) is the nonuniform usage of codons, occurring often in nearly all organisms. Our previous study found that SCUB is correlated with intron number, is unequal among exons in the plant nuclear genome, and mirrors evolutionary specialization. However, whether this rule exists in the plastid genome has not been addressed. Here, we present an analysis of SCUB in the plastid genomes of 25 species from lower to higher plants (algae, bryophytes, pteridophytes, gymnosperms, and spermatophytes). We found NNA and NNT (A- and T-ending codons) are preferential in the plastid genomes of all plants. Interestingly, this preference is heterogeneous among taxonomies of plants, with the strongest preference in bryophytes and the weakest in pteridophytes, suggesting an association between SCUB and plant evolution. In addition, SCUB frequencies are consistent among genes with varied introns and among exons, indicating that the bias of NNA and NNT is unrelated to either intron number or exon position. Further, SCUB is associated with DNA methylation–induced conversion of cytosine to thymine in the vascular plants but not in algae or bryophytes. These data demonstrate that these SCUB profiles in the plastid genome are distinctly different compared with the nuclear genome. PMID:25922569

  10. [Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

    PubMed

    Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

    2013-08-01

    Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

  11. Discrete conductance switching in conducting polymer wires

    NASA Astrophysics Data System (ADS)

    He, H. X.; Li, X. L.; Tao, N. J.; Nagahara, L. A.; Amlani, I.; Tsui, R.

    2003-07-01

    Charge transport in conducting polymers (polyaniline and polypyrrole) bridged between two gold nanoelectrodes separated with a nanoscale gap (varying from ˜1 nm to a few tens of nm was studied by controlling the polymer redox states electrochemically. In sharp contrast to the macroscopic samples, the conductance switches abruptly between insulating (off) and conducting (on) states like a telegraphic signal. The time durations of the on and off states depend on the potential of the nanoelectrodes, indicating the important role of the redox states in the signal. We attribute the telegraphic signal to the fluctuation between the insulating reduced state and conducting oxidized state of the polymer, which rises as electrons trap into the oxidized state and escape from the reduced state.

  12. Conducting Compositions of Matter

    NASA Technical Reports Server (NTRS)

    Viswanathan, Tito (Inventor)

    2001-01-01

    The invention provides conductive compositions of matter, as well as methods for the preparation of the conductive compositions of matter, solutions comprising the conductive compositions of matter, and methods of preparing fibers or fabrics having improved anti-static properties employing the conductive compositions of matter.

  13. Conducting Compositions of Matter

    NASA Technical Reports Server (NTRS)

    Viswanathan, Tito (Inventor)

    1999-01-01

    The invention provides conductive compositions of matter, as well as methods for the preparation of the conductive compositions of matter, solutions comprising the conductive compositions of matter, and methods of preparing fibers or fabrics having improved anti-static properties employing the conductive compositions of matter.

  14. Conducting compositions of matter

    NASA Technical Reports Server (NTRS)

    Viswanathan, Tito (Inventor)

    2000-01-01

    The invention provides conductive compositions of matter, as well as methods for the preparation of the conductive compositions of matter, solutions comprising the conductive compositions of matter, and methods of preparing fibers or fabrics having improved anti-static properties employing the conductive compositions of matter.

  15. Small RNA populations for two unrelated viruses exhibit different biases in strand polarity and proximity to terminal sequences in the insect host Homalodisca vitripennis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Next generation sequencing was used to analyze virus-derived small RNA (vsRNA) profiles for two taxonomically unrelated viruses infecting Homalodisca vitripennis, the glassy winged sharpshooter. Homalodisca coagulata virus-1 (HoCV-1), family Dicistroviridae, and Homalodisca vitripennis virus (HoVRV)...

  16. A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses

    PubMed Central

    2012-01-01

    Background Viruses are known to be the most abundant organisms on earth, yet little is known about their collective origin and evolutionary history. With exceptionally high rates of genetic mutation and mosaicism, it is not currently possible to resolve deep evolutionary histories of the known major virus groups. Metagenomics offers a potential means of establishing a more comprehensive view of viral evolution as vast amounts of new sequence data becomes available for comparative analysis. Results Bioinformatic analysis of viral metagenomic sequences derived from a hot, acidic lake revealed a circular, putatively single-stranded DNA virus encoding a major capsid protein similar to those found only in single-stranded RNA viruses. The presence and circular configuration of the complete virus genome was confirmed by inverse PCR amplification from native DNA extracted from lake sediment. The virus genome appears to be the result of a RNA-DNA recombination event between two ostensibly unrelated virus groups. Environmental sequence databases were examined for homologous genes arranged in similar configurations and three similar putative virus genomes from marine environments were identified. This result indicates the existence of a widespread but previously undetected group of viruses. Conclusions This unique viral genome carries implications for theories of virus emergence and evolution, as no mechanism for interviral RNA-DNA recombination has yet been identified, and only scant evidence exists that genetic exchange occurs between such distinct virus lineages. Reviewers This article was reviewed by EK, MK (nominated by PF) and AM. For the full reviews, please go to the Reviewers' comments section. PMID:22515485

  17. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia.

    PubMed

    Ruggeri, A; Labopin, M; Sanz, G; Piemontese, S; Arcese, W; Bacigalupo, A; Blaise, D; Bosi, A; Huang, H; Karakasis, D; Koc, Y; Michallet, M; Picardi, A; Sanz, J; Santarone, S; Sengelov, H; Sierra, J; Vincent, L; Volt, F; Nagler, A; Gluckman, E; Ciceri, F; Rocha, V; Mohty, M

    2015-09-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need.

  18. Global synchronous changes in the carbon isotopic composition of carbonate sediments unrelated to changes in the global carbon cycle

    PubMed Central

    Swart, Peter K.

    2008-01-01

    The carbon isotopic (δ13C) composition of bulk carbonate sediments deposited off the margins of four carbonate platforms/ramp systems (Bahamas, Maldives, Queensland Plateau, and Great Australian Bight) show synchronous changes over the past 0 to 10 million years. However, these variations are different from the established global pattern in the δ13C measured in the open oceans over the same time period. For example, from 10 Ma to the present, the δ13C of open oceanic carbonate has decreased, whereas platform margin sediments analyzed here show an increase. It is suggested that the δ13C patterns in the marginal platform deposits are produced through admixing of aragonite-rich sediments, which have relatively positive δ13C values, with pelagic materials, which have lower δ13C values. As the more isotopically positive shallow-water carbonate sediments are only produced when the platforms are flooded, there is a connection between changes in global sea level and the δ13C of sediments in marginal settings. These data indicate that globally synchronous changes in δ13C can take place that are completely unrelated to variations in the global carbon cycle. Fluctuations in the δ13C of carbonate sediments measured during previous geological periods may also be subject to similar processes, and global synchroniety of δ13C can no longer necessarily be considered an indicator that such changes are related to, or caused by, variations in the burial of organic carbon. Inferences regarding the interpretation of changes in the cycling of organic carbon derived from δ13C records should be reconsidered in light of the findings presented here. PMID:18772393

  19. Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated caucasian individuals: Correlation with phenotypic activity

    SciTech Connect

    Cascorbi, I.; Drakoulis, N.; Brockmoeller, J.

    1995-09-01

    The polymorphic arylamine N-acetyltransferase (NAT2; EC2.3.1.5) is supposed to be a susceptibility factor for several drug side effects and certain malignancies. A group of 844 unrelated German subjects was genotyped for their acetylation type, and 563 of them were also phenotyped. Seven mutations of the NAT2 gene were evaluated by allele-specific PCR (mutation 341C to T) and PCR-RFLP for mutations at nt positions 191, 282, 481, 590, 803, and 857. From the mutation pattern eight different alleles, including the wild type coding for rapid acetylation and seven alleles coding for slow phenotype, were determined. Four hundred ninety-seven subjects had a genotype of slow acetylation (58.9%; 95% confidence limits 55.5%-62.2%). Phenotypic acetylation capacity was expressed as the ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after caffeine intake. Some 6.7% of the cases deviated in genotype and phenotype, but sequencing DNA of these probands revealed no new mutations. Furthermore, linkage pattern of the mutations was always confirmed, as tested in 533 subjects. In vivo acetylation capacity of homozygous wild-type subjects (NAT2{sup *}4/{sup *}4) was significantly higher than in heterozygous genotypes (P = .001). All mutant alleles showed low in vivo acetylation capacities, including the previously not-yet-defined alleles {sup *}5A, {sup *}5C, and {sup *}13. Moreover, distinct slow genotypes differed significantly among each other, as reflected in lower acetylation capacity of {sup *}6A, {sup *}7B, and {sup *}13 alleles than the group of {sup *}5 alleles. The study demonstrated differential phenotypic activity of various NAT2 genes and gives a solid basis for clinical and molecular-epidemiological investigations. 34 refs., 4 figs., 7 tabs.

  20. De novo interstitial deletions of 9q22.1-22.3 in two unrelated cases with different phenotype

    SciTech Connect

    Mohamed, A.N.; Bawle, E.; Conard, J.

    1994-09-01

    Deletions involving the long arm of chromosome 9 are rare. A recent review, particularly with deletions of 9q22-32 region, failed to recognize a distinct pattern of dysmorphies and malformations. Herein, we described two phenotypically abnormal unrelated cases with interstitial deletion of chromosome 9 at band q22.1-q22.3. Parents of both cases exhibited normal karyotypes, indicating that the deletions were de novo events. Therefore, the clinical features present in these two cases can be attributed to partial monosomy for the deleted band 9q22. The first case was a 2-day-old baby with ambiguous genitalia, hydrocephalus, cleft palate and lip, polycystic kidney, absence of uterus on ultrasound and one gonad in the labiosacral region. Chromosome analysis showed a male karyotype, 46,XY,del(9)(q22.1q22.3). The absence of monosomy X cell line and the normal histology of testicular tissue were against the diagnosis of mixed gonadal dysgenesis or XY gonadal dysgenesis. The second 3-day-old newborn baby girl presented with right side hypoplastic heart and pulmonary atresia. In addition, the patient showed multiple dysmorphic features including epicanthal fold, low-set ears, depressed nasal bridge, hypertelorism, and micrognathia. The uvula is absent with slight cleft palate. Bilateral clinodactyly of 5th fingers and severe club feet were also present. The external genitalia was of a normal female phenotype. Chromosome study also indicated interstatial deletion of band 9q22. Although both cases appeared to have the same chromosomal anomalies, neither a discrete facial appearance nor a common pattern of malformations was noted.

  1. Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation.

    PubMed

    Thomson, B G; Robertson, K A; Gowan, D; Heilman, D; Broxmeyer, H E; Emanuel, D; Kotylo, P; Brahmi, Z; Smith, F O

    2000-10-15

    Unrelated cord blood (UCB) is being used as a source of alternative hematopoietic stem cells for transplantation with increasing frequency. From November 1994 to February 1999, 30 UCB transplant procedures were performed for both malignant and nonmalignant diseases in 27 children, aged 0.4 to 17.1 years. Patients received either HLA-matched (n = 3) or 1- or 2-antigen-mismatched (n = 27) UCB following 1 of 2 standardized preparative and graft-versus-host disease regimens (hyperfractionated total body irradiation, cyclophosphamide, and antithymocyte globulin [ATG] with cyclosporine A and methotrexate; or busulfan, melphalan, and ATG with cyclosporine A and prednisone). The median time to neutrophil and platelet engraftment was 27 days (12-60 days) and 75 days (33-158 days) posttransplantation, respectively. No correlation was noted between neutrophil and platelet engraftment and nucleated cells per kilogram, CD34(+) cells per kilogram infused, or cytomegalovirus status of recipient. The cumulative probability of acute grade 2 or greater graft-versus-host disease (GVHD) was 37.2%, and of grade 3 or greater GVHD was 8.8%. No patients developed chronic GVHD. CD4, CD19, and natural killer cell recovery was achieved at a median of 12, 6, and 2 months, respectively. CD8 recovery was delayed at a median of 9 months. Normal mitogen response was achieved at 6 to 9 months. The probability of survival, disease-free survival, and event-free survival at 1 year was 52.3% (34.1%-70.5%), 54.7% (34.5%-74.9 %) and 49.6% (29.9%-69.4%), respectively. This series of 30 UCB transplants suggests that although CD8 cell recovery is delayed, the pattern of immune reconstitution with UCB is similar to that reported for other stem cell sources. (Blood. 2000;96:2703-2711)

  2. Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors.

    PubMed

    Molloy, K; Goulden, N; Lawler, M; Cornish, J; Oakhill, A; Pamphilon, D; Potter, M; Steward, C; Langlands, K; Humphries, P; McCann, S R

    1996-04-01

    Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.

  3. Impact of hematopoietic chimerism at day +14 on engraftment after unrelated donor umbilical cord blood transplantation for hematologic malignancies

    PubMed Central

    Moscardó, Federico; Sanz, Jaime; Senent, Leonor; Cantero, Susana; de la Rubia, Javier; Montesinos, Pau; Planelles, Dolores; Lorenzo, Ignacio; Cervera, Jose; Palau, Javier; Sanz, Miguel A.; Sanz, Guillermo F.

    2009-01-01

    Background Cord blood transplant is a feasible treatment alternative for adult patients with hematologic malignancies lacking a suitable HLA-matched donor. However, the kinetics of myeloid recovery is slow, and primary graft failure cannot be detected easily early after transplantation. We investigated the impact of hematopoietic chimerism status from unselected marrow cells 14 days after transplantation on predicting engraftment after a cord blood transplant. Design and Methods Seventy-one adult patients with hematologic malignancies undergoing single-unit unrelated donor cord blood transplantation after a myeloablative conditioning regimen were included in the study. All patients received conditioning regimens based on busulfan, thiotepa and antithymocyte globulin. Chimerism status was assessed analyzing short tandem repeat polymorphisms. Results The cumulative incidence of myeloid engraftment at 1 month was significantly lower in patients with mixed chimerism than in those with complete donor chimerism (55% vs. 94%; p<0.0001). For patients achieving myeloid recovery, the median time of engraftment was 16 days when donor chimerism at day + 14 was higher than 90%, compared with 24 days when donor chimerism was below this level (p<0.001). A donor chimerism level of 65% was found to be the best cut-off point for predicting primary graft failure, with a sensitivity of 97% and a specificity of 80%. The incidence of primary graft failure was 67% for patients with less than 65% donor chimerism at day +14 as compared to only 2% for those with more than 65% donor chimerism (p<0.001). Patients with mixed chimerism also had a lower cumulative incidence of platelet engraftment than those with complete chimerism (62% vs. 89%; p=0.01). Conclusions Donor-recipient chimerism status at day +14 predicts engraftment after a single-unit cord blood transplant in adults. PMID:19483157

  4. The range of chronic demyelinating neuropathy of infancy: a clinico-pathological and genetic study of 15 unrelated cases.

    PubMed

    Planté-Bordeneuve, V; Parman, Y; Guiochon-Mantel, A; Alj, Y; Deymeer, F; Serdaroglu, P; Eraksoy, M; Said, G

    2001-09-01

    The concept of Dejerine-Sottas disease, which corresponds to presumed recessive demyelinating neuropathies with onset in infancy, remains controversial. To learn more on the subject, we performed a clinico-pathological and molecular genetic study in 15 unrelated patients with the Dejerine-Sottas phenotype seen over a 16 year period. There were 12 females and 3 males, born to asymptomatic parents. Study of the PMP22, P0 and Egr2 genes was performed in all cases and 14 underwent a nerve biopsy. First manifestations of neuropathy occurred before 3 years of age in all patients. An inherited disorder was suspected in 10 patients, because of their family history and/or disclosure of a molecular genetic defect in 4 of them. One patient had a recessively transmitted homozygous point mutation (Arg157Trp) of the PMP22 gene. A heterozygous duplication of the 17p11.2-12 segment was detected in one offspring of a consanguineous marriage. One patient carried a "de novo" heterozygous Ser72Leu substitution in the PMP22. A heterozygous double mutation of the P0 gene including a "de novo" Val42 deletion and an Ala221Thr substitution, maternally inherited, were found in an apparently sporadic case. No mutation of the Egr2 gene was identified. A neuropathy with focally folded myelin sheaths (CMT4B) was diagnosed in the nerve biopsy specimens of two patients. In five patients, the clinico-pathological findings along with the absence of an identified mutation suggested the diagnosis of chronic inflammatory demyelinating polyneuropathy of infantile onset. Our findings illustrate the genetic heterogeneity of cases with identified mutations, the scarcity of cases with "demonstrated" recessive transmission and the likelihood of early acquired chronic inflammatory demyelinating polyneuropathy in several patients. PMID:11596785

  5. Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy.

    PubMed Central

    Schena, F P; Scivittaro, V; Ranieri, E; Sinico, R; Benuzzi, S; Di Cillo, M; Aventaggiato, L

    1993-01-01

    In the last few years many investigators have reported the recurrence of primary IgA nephropathy (IgAN) or the presence of persistent microhaematuria and/or proteinuria in family members of patients with IgAN. Our study was undertaken to investigate the relevance of abnormalities in the regulation of the IgA and IgM immune system in microhaematuric and asymptomatic family members of IgAN patients. Fifty-four out of 120 members of nine unrelated pedigrees were examined by urinalysis; polymeric IgA (pIgA), IgA rheumatoid factor (IgARF), IgA1-IgG immune complexes (IgA 1-IgG IC) and IgA 1-IgM IC, and other immunoglobulins were measured in serum samples. Moreover, we studied the production of immunoglobulins, pIgA and IgARF by peripheral blood mononuclear cells (PBMC) in basal conditions and after pokeweed mitogen (PWM) stimulation. Our data demonstrate that persistent microhaematuria was present in 24% of relatives. High serum levels of IgA, mainly pIgA and IgARF, IgA 1-IgG IC and IgA 1-IgM IC occurred in 66% of relatives. Abnormal spontaneous production of IgA by PBMC and after PWM stimulation was present in 64% of family members. Interestingly, high serum levels of IgM and abnormal production of this immunoglobulin by PBMC were observed in relatives. However, the immunological abnormalities did not correlate in any way with the presence of urinary abnormalities such as microhaematuria, which was most likely determined by an underlying glomerular alteration. PMID:8467558

  6. How do fast impulse CMEs related to powerful flares but unrelated to eruptive filaments appear and move?

    NASA Astrophysics Data System (ADS)

    Zagainova, Iu. S.; Fainshtein, V. G.

    2015-02-01

    GOES-12/SXI and SDO/AIA data were used to examine the formation and initial stage of movement for several fast pulse 'halo'-type coronal mass ejections (HCMEs) that were related to GOES M and X class flares but unrelated to solar filament eruptions. According to their formation, the HCMEs under study can be subdivided into three groups: (i) Most of the HCMEs studied resulted from broken equilibrium - presumably, due to an emerging new magnetic flux - of solitary wide loop-like emission structures identified with the future ejection observable in the 195 Å channel a few hours before the mass ejection starts moving or before the relevant flare onset; (ii) a CME can form from several individual loop-like structures or, possibly, a loop arcade; (iii) for some HCMEs, their formation starts with a group of coronal loops moving upwards as first observed in the 'hot' 131 Å channel. A few minutes later, loops start to move observable in images taken with the 'colder' 211 Å channel, still later in the 193 Å channel, and finally, in 171 Å channel images. The moving loop-like structures affect the overlying coronal areas in such a way that a frontal HCME structure forms, its brightness increasing from the 'hottest' to the 'coldest' line. Moreover, loops are observed moving sunwards, towards the CME origin, resulting in an area of lower brightness forming behind the frontal structure. All the coronal mass ejections we studied started to move before the related solar flares appeared. The kinematics of the HCME's under examination has been studied along, generally, curvilinear trajectories in the plane-of-sky. It has been concluded that two types of coronal mass ejections exist differing in their time speed profile determined by the area and magnetic configuration of the active area where the mass ejection originated. Homologous HCMEs - i.e. appearing in the same active area at different times - have the same speed profile.

  7. Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men.

    PubMed

    Perez-Mora, Nicolas; Velasco, Carlos; Bermüdez, Fernando

    2015-01-01

    Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long-term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT. A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response. A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single-therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido). The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03). FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients. PMID:26380503

  8. Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His.

    PubMed

    Luo, Meiling; Deng, Donghong; Xiang, Liqun; Cheng, Peng; Liao, Lin; Deng, Xuelian; Yan, Jie; Lin, Faquan

    2016-09-01

    Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS-PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS-PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen. PMID:27684817

  9. Cardiac conduction system

    MedlinePlus

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  10. The Conductivity of Solutions.

    ERIC Educational Resources Information Center

    Rayner-Canham, Geoff

    1993-01-01

    Presents historical background and modern explanations for the popular demonstration of showing conductivity of solutions through the insertion of a light-bulb conductivity tester into deionized water and water with salt in it. (PR)

  11. Limits of proton conductivity.

    PubMed

    Kreuer, Klaus-Dieter; Wohlfarth, Andreas

    2012-10-15

    Parasitic current seems to be the cause for the "highest proton conductivity" of a material reported to date. Kreuer and Wohlfarth verify this hypothesis by measuring the conductivity of the same materials after preparing them in a different way. They further explain the limits of proton conductivity and comment on the problems of determining the conductivity of small objects (e.g., whiskers, see picture).

  12. Surface Conductive Glass.

    ERIC Educational Resources Information Center

    Tanaka, John; Suib, Steven L.

    1984-01-01

    Discusses the properties of surface-conducting glass and the chemical nature of surface-conducting stannic (tin) oxide. Also provides the procedures necessary for the preparation of surface-conducting stannic oxide films on glass substrates. The experiment is suitable for the advanced inorganic chemistry laboratory. (JN)

  13. Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Recovery of Unrelated Donors of Bone Marrow: A Prespecified Analysis from the Phase III Blood and Marrow Transplant Clinical Trials Network Protocol 0201.

    PubMed

    Burns, Linda J; Logan, Brent R; Chitphakdithai, Pintip; Miller, John P; Drexler, Rebecca; Spellman, Stephen; Switzer, Galen E; Wingard, John R; Anasetti, Claudio; Confer, Dennis L

    2016-06-01

    We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P < .001). Other characteristics that significantly increased the likelihood of complete recovery were being an international donor and donation in more recent years. Donors of BM were more likely to report grades 2 to 4 skeletal pain, body symptoms, and fatigue at 1 week after donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 after collection of BM donors) could be analyzed, no variable was significantly associated with grades 2 to 4 skeletal pain, including product donated (BM versus PBSC; odds ratio, 1.13; 95% CI, .74 to 1.74; P = .556). Blood counts were affected by product donated, with greater mean change from baseline to after donation for white blood cells, neutrophils, mononuclear cells, and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as

  14. Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Recovery of Unrelated Donors of Bone Marrow: A Prespecified Analysis from the Phase III Blood and Marrow Transplant Clinical Trials Network Protocol 0201.

    PubMed

    Burns, Linda J; Logan, Brent R; Chitphakdithai, Pintip; Miller, John P; Drexler, Rebecca; Spellman, Stephen; Switzer, Galen E; Wingard, John R; Anasetti, Claudio; Confer, Dennis L

    2016-06-01

    We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P < .001). Other characteristics that significantly increased the likelihood of complete recovery were being an international donor and donation in more recent years. Donors of BM were more likely to report grades 2 to 4 skeletal pain, body symptoms, and fatigue at 1 week after donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 after collection of BM donors) could be analyzed, no variable was significantly associated with grades 2 to 4 skeletal pain, including product donated (BM versus PBSC; odds ratio, 1.13; 95% CI, .74 to 1.74; P = .556). Blood counts were affected by product donated, with greater mean change from baseline to after donation for white blood cells, neutrophils, mononuclear cells, and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as

  15. Cermet fuel thermal conductivity

    SciTech Connect

    Peddicord, K.L. ); Alvis, J.M. Jr.; Thomas, J.K.

    1991-01-01

    Cermets have been proposed as a candidate fuel for space reactors for several reasons, including their potential for high thermal conductivity. However, there is currently no accepted model for cermet fuel thermal conductivity. The objective of the work reported in this paper was to (a) investigate the adequacy of existing models; (b) develop, if necessary, an improved model; and (c) provide recommendations for future work on cermet thermal conductivity. The results from this work indicate that further work is needed to accurately characterize cermet fuel thermal conductivity. It was determined that particle shape and orientation have a large impact on cermet thermal conductivity.

  16. Electrically conductive composite material

    DOEpatents

    Clough, R.L.; Sylwester, A.P.

    1988-06-20

    An electrically conductive composite material is disclosed which comprises a conductive open-celled, low density, microcellular carbon foam filled with a non-conductive polymer or resin. The composite material is prepared in a two-step process consisting of first preparing the microcellular carbon foam from a carbonizable polymer or copolymer using a phase separation process, then filling the carbon foam with the desired non-conductive polymer or resin. The electrically conductive composites of the present invention has a uniform and consistent pattern of filler distribution, and as a result is superior over prior art materials when used in battery components, electrodes, and the like. 2 figs.

  17. Electrically conductive composite material

    DOEpatents

    Clough, Roger L.; Sylwester, Alan P.

    1989-01-01

    An electrically conductive composite material is disclosed which comprises a conductive open-celled, low density, microcellular carbon foam filled with a non-conductive polymer or resin. The composite material is prepared in a two-step process consisting of first preparing the microcellular carbon foam from a carbonizable polymer or copolymer using a phase separation process, then filling the carbon foam with the desired non-conductive polymer or resin. The electrically conductive composites of the present invention has a uniform and consistant pattern of filler distribution, and as a result is superior over prior art materials when used in battery components, electrodes, and the like.

  18. Unrelated transplantation for poor-prognosis adult acute lymphoblastic leukemia: long-term outcome analysis and study of the impact of hematopoietic graft source.

    PubMed

    Ferrá, Christelle; Sanz, Jaime; de la Cámara, Rafael; Sanz, Guillermo; Bermúdez, Arancha; Valcárcel, David; Rovira, Montserrat; Serrano, David; Caballero, Dolores; Espigado, Ildefonso; Morgades, Mireia; Heras, Inmaculada; Solano, Carlos; Duarte, Rafael; Barrenetxea, Cristina; García-Noblejas, Ana; Díez-Martin, José L; Iriondo, Arturo; Carreras, Enric; Sierra, Jordi; Sanz, Miguel-Angel; Ribera, Josep-Maria

    2010-07-01

    Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated stem cell transplantation (SCT) if a matched sibling donor is not available. We analyzed the outcome of adult patients with unrelated SCT for HR-ALL and studied the possible effect of the hematopoietic stem cell source of the transplant. A total of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007. Patients in first complete remission (CR1) at transplantation had at least one adverse prognostic factor (advanced age, adverse cytogenetics, hyperleukocytosis, or slow response to induction therapy). ALL was in CR1 in 81 patients (54%), in second CR (CR2) in 37 patients (25%), in third CR (CR3) in 11 patients (7%), and with overt disease in 20 patients (13%). The hematopoietic source was unrelated cord blood (UCB) in 62 patients and an unrelated donor (UD) in 87 patients. The patients undergoing UCB-SCT and UD-SCT were comparable in terms of the main clinical and biological features of ALL, except for a higher frequency of patients with more overt disease in the UCB-SCT group. There was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) at 5 years between the 2 groups. Treatment-related mortality (TRM) was significantly lower in the UCB-SCT group (P = .021). The probability of relapse at 1 year was 17% (95% confidence interval [CI], 7%-27%) for the UD-SCT group and 27% (95% CI, 14%-40%) for the UCB-SCT group (P = .088), respectively. Only disease status at transplantation (CR1, 41% [95% CI, 18%-64%] vs CR2, 51% [95% CI, 17%-85%] vs advanced disease, 66% [95% CI, 46%-86%]; P = .001) and the absence of chronic graft-versus-host disease (74% [95% CI, 46%-100%] vs 33% [95% CI, 17%-49%]; P = .034) were significant factors for relapse. All unrelated transplantation modalities were associated with high

  19. Staphylococcal Enterotoxin B (SEB) Induces Memory CD4 T Cell Anergy in vivo and Impairs Recall Immunity to Unrelated Antigens

    PubMed Central

    Janik, David K; Lee, William T

    2015-01-01

    Introduction Naïve and memory T cells can utilize unique regulatory pathways to promote protection but prevent self-reactivity. A bacterial superantigen SEB exploits unique TCR proximal signaling processes in memory CD4 T cells to induce clonal anergy. The aim of this study was to determine if SEB could antagonize memory CD4 T cells in vivo and whether there would be consequences on recall immune responses. We evaluated Ab responses to a T-dependent antigen as a measurement of memory T cell helper function. Method BALB/c mice were primed with TNP-RGG to elicit memory B cells and also immunized with an ovalbumin peptide to elicit memory helper T cells. Another group of TNP-RGG immunized mice were used as adoptive transfer recipients of exogenous DO11.10 memory T cells. Mice were challenged with TNP-OVA with or without prior administration of SEB. B cells secreting IgM or IgG TNP-specific Ab were enumerated by ELISPOT as indicators of primary versus secondary humoral immunity. Results Comparing the SEB and non-SEB-treated groups, the SEB-treated group failed to produce TNP-specific IgG in response to challenge with TNP-OVA, even if they were previously immunized with OVA. All groups produced IgM, indicating that the primary Ab responses and naïve helper T cells were not impacted by SEB. SEB had no negative impact when DO11.10 × Fyn−/− memory T cells were used as donor cells. Conclusion The present study indicated that SEB selectively targeted memory CD4 T cells in vivo and prevented helper function. Consequently, recall humoral immunity was lost. The data are most consistent with in vivo T cell anergy as opposed to indirect suppression as elimination of Fyn kinase restored helper function. These data suggest that bacterial superantigens can impair post-vaccination memory cell responses to unrelated antigens via their ability to target Vb families and antagonize memory cell activation. PMID:26807307

  20. A Comparison of Outcomes for Cord Blood Transplantation and Unrelated Bone Marrow Transplantation in Adult Aplastic Anemia.

    PubMed

    Kuwatsuka, Yachiyo; Kanda, Junya; Yamazaki, Hirohito; Mori, Takehiko; Miyamura, Koichi; Kako, Shinichi; Uchida, Naoyuki; Ohashi, Kazuteru; Ozawa, Yukiyasu; Takahashi, Yoshiyuki; Kato, Chiaki; Iwato, Koji; Ishiyama, Ken; Kobayashi, Hikaru; Eto, Tetsuya; Kahata, Kaoru; Kato, Jun; Miyamoto, Toshihiro; Kato, Koji; Mori, Shinicihro; Atsuta, Yoshiko; Kimura, Fumihiko; Kanda, Yoshinobu

    2016-10-01

    Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8-matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio [HR], .55; 95% confidence interval [CI], .32 to .94; P = .029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR, .55; 95% CI, .29 to 1.02) or 6/8-matched UBMT (HR, .67; 95% CI, .32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old,survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. PMID:27401034

  1. Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO).

    PubMed

    Dini, G; Cancedda, R; Locatelli, F; Bosi, A; Bandini, G; Alessandrino, E P; Porta, F; Uderzo, C; Messina, C; Fagioli, F; Arcese, W; Marenco, P; Fanin, R; Falda, M; Soligo, D; La Nasa, G; Giardini, C; Pession, A; Scimè, R; Di Bartolomeo, P; Bruno, B; Garbarino, L; Lamparelli, T; Giorgiani, G; Lanino, E; Manzitti, C; Bacigalupo, A

    2000-11-01

    Unrelated donor bone marrow transplant (UD-BMT) has become an attractive alternative source of hematopoietic cells for patients lacking a matched sibling. The aim of this paper was to report on results of the 696 UD BMTs performed in 31 Italian institutions during the first 10 years of activity of the Italian Bone Marrow Donor Registry (IBMDR). In 1989 the Italian Bone Marrow Transplant Group (GITMO) established the IBMDR to facilitate donor search and marrow procurement for patients lacking an HLA identical sibling. By end of December 1999, 260,000 HLA-A, B typed volunteer donors had been cumulatively registered and 2,620 searches had been activated for Italian patients. At least one HLA-A, B, DRB1 matched donor was found for 54% of the patients and 696 UD BMTs were performed. In 50% of cases the donor was found in the IBMDR and in 50% in 15 other Registries. The average time from search activation to transplant was 6 months for disease other than CML. For CML it was 14 months. Actuarial 12-month transplant-related mortality (TRM) was 68% in patients grafted between 1979 and 1992 and 44% for patients grafted after 1993. Twenty-eight per cent of patients developed grade III or IV acute GvHD and 24% developed extensive chronic GvHD. The rate of disease free survival at three years was 57% for patients with 1st chronic phase CML, 37% for patients with 1st or 2nd CR ALL, 31% for AML or MDS patients < or = 18 years of age and 54% for patients with inborn errors. We conclude that the IBMDR has benefited a substantial number of patients lacking a matched sibling and has facilitated the recruitment of UDs into the international donor pool. The long time required for the search is the major obstacle to the success of this programme. This suggests that early transplant and a decrease in TRM could further improve these encouraging results.

  2. High conductance surge cable

    DOEpatents

    Murray, Matthew M.; Wilfong, Dennis H.; Lomax, Ralph E.

    1998-01-01

    An electrical cable for connecting transient voltage surge suppressers to ectrical power panels. A strip of electrically conductive foil defines a longitudinal axis, with a length of an electrical conductor electrically attached to the metallic foil along the longitudinal axis. The strip of electrically conductive foil and the length of an electrical conductor are covered by an insulating material. For impedance matching purposes, triangular sections can be removed from the ends of the electrically conductive foil at the time of installation.

  3. High conductance surge cable

    DOEpatents

    Murray, M.M.; Wilfong, D.H.; Lomax, R.E.

    1998-12-08

    An electrical cable for connecting transient voltage surge suppressors to electrical power panels. A strip of electrically conductive foil defines a longitudinal axis, with a length of an electrical conductor electrically attached to the metallic foil along the longitudinal axis. The strip of electrically conductive foil and the length of an electrical conductor are covered by an insulating material. For impedance matching purposes, triangular sections can be removed from the ends of the electrically conductive foil at the time of installation. 6 figs.

  4. Electrically conductive cellulose composite

    DOEpatents

    Evans, Barbara R.; O'Neill, Hugh M.; Woodward, Jonathan

    2010-05-04

    An electrically conductive cellulose composite includes a cellulose matrix and an electrically conductive carbonaceous material incorporated into the cellulose matrix. The electrical conductivity of the cellulose composite is at least 10 .mu.S/cm at 25.degree. C. The composite can be made by incorporating the electrically conductive carbonaceous material into a culture medium with a cellulose-producing organism, such as Gluconoacetobacter hansenii. The composites can be used to form electrodes, such as for use in membrane electrode assemblies for fuel cells.

  5. Comparison of Outcomes of HLA-Matched Related, Unrelated, or HLA-Haploidentical Related Hematopoietic Cell Transplantation following Nonmyeloablative Conditioning for Relapsed or Refractory Hodgkin Lymphoma

    PubMed Central

    Burroughs, Lauri M.; O’Donnell, Paul V.; Sandmaier, Brenda M.; Storer, Barry E.; Luznik, Leo; Symons, Heather J.; Jones, Richard J.; Ambinder, Richard F.; Maris, Michael B.; Blume, Karl G.; Niederwieser, Dietger W.; Bruno, Benedetto; Maziarz, Richard T.; Pulsipher, Michael A.; Petersen, Finn B.; Storb, Rainer; Fuchs, Ephraim J.; Maloney, David G.

    2008-01-01

    We compared the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for patients with relapsed or refractory Hodgkin lymphoma (HL) based on donor cell source. Ninety patients with HL were treated with nonmyeloablative conditioning followed by HCT from HLA-matched related, n = 38, unrelated, n = 24, or HLA-haploidentical related, n = 28 donors. Patients were heavily pretreated with a median of 5 regimens and most patients had failed autologous HCT (92%) and local radiation therapy (83%). With a median follow-up of 25 months, 2-year overall survivals, progression-free survivals (OS)/(PFS), and incidences of relapsed/progressive disease were 53%, 23%, and 56% (HLA-matched related), 58%, 29%, and 63% (unrelated), and 58%, 51%, and 40% (HLA-haploidentical related), respectively. Nonrelapse mortality (NRM) was significantly lower for HLA-haploidentical related (P =.02) recipients compared to HLA-matched related recipients. There were also significantly decreased risks of relapse for HLA-haploidentical related recipients compared to HLA-matched related (P = .01) and unrelated (P = .03) recipients. The incidences of acute grades III–IV and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 16%/50% (HLA-matched related), 8%/63% (unrelated), and 11%/35% (HLA-haploidentical related). These data suggested that salvage allogeneic HCTusing nonmyeloablative conditioning provided antitumor activity in patients with advanced HL; however, disease relapse/progression continued to be major problems. Importantly, alternative donor stem cell sources are a viable option. PMID:18940683

  6. Detection of a New Community Genotype Methicillin-Resistant Staphylococcus aureus Clone That Is Unrelated to the USA300 Clone and That Causes Pediatric Infections in Colombia

    PubMed Central

    Marquez-Ortiz, Ricaurte Alejandro; Alvarez-Olmos, Martha I.; Leal, Aura Lucia; Castro, Betsy Esperanza; Vanegas, Natasha

    2013-01-01

    The dissemination of a clone of community genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) that is related to USA300 has been reported in Latin America. We recently detected isolates of a new clone of CG-MRSA (spa type t1635 and ACME-negative) that was genetically unrelated to the USA300 clone and that causes infections in children in Colombia. This finding indicates the appearance of a new clone of CG-MRSA in our region. PMID:23241375

  7. [Genetic polymorphisms of Y-STR haplotypes in unrelated male blood donors from the surname of Li, Wang and Zhang population in Shenzhen].

    PubMed

    Deng, Zhi-Hui; Li, Qian; Wang, Da-Ming; Gao, Su-Qing; Zeng, Jian-Qiang

    2007-11-01

    To study the genetic polymorphisms of Y-chromosome-specific STR loci in Chinese of different surnames, 9 Y-STR loci were amplified by single fluorescent multiplex PCR and the PCR products were detected by using ABI PrismTM 3100 DNA Sequencer. Samples were randomly-selected from male blood donors in ShenZhen. These individuals, who were otherwise unrelated, had the most common surnames among Chinese as their surnames, namely Li, Wang or Zhang. There were 139 subjects with surname Li, 118 with surname Wang and 119 with the surname Zhang. In the Li population, a total of 126 haplotypes was found and 118 of them were unique, with a haplotype diversity 0.9974. In the Wang population, a total of 105 haplotypes was found and 94 of them were unique, with a haplotype diversity of 0.9953. In the Zhang population, a total of 101 haplotypes was found and 88 of them were unique, with a haplotype diversity of 0.9964. Our results indicated that the genetic polymorphisms of Y-STR haplotypes at these 9 loci in unrelated male individuals with Chinese surnames of Li, Wang or Zhang are highly polymorphic and showed no significant differences with our previous data of haplotype polymorphisms in unrelated male individuals from the Chinese ethnic Han population.

  8. Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma.

    PubMed

    El-Cheikh, Jean; Crocchiolo, Roberto; Boher, Jean-Marie; Furst, Sabine; Stoppa, Anne-Marie; Ladaique, Patrick; Faucher, Catherine; Calmels, Boris; Castagna, Luca; Lemarie, Claude; De Colella, Jean-Marc Schiano; Coso, Diane; Bouabdallah, Reda; Chabannon, Christian; Blaise, Didier

    2012-06-01

    The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% (P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols.

  9. HIV-unrelated benign lymphoepithelial cyst of the parotid glands containing lymphoepithelial lesion--like structures: a report of 3 cases.

    PubMed

    Kojima, Masaru; Nakamura, Naoya; Matsuda, Hazuki; Kaba, Sadayuki; Itoh, Hideaki; Masawa, Nobuhide

    2009-12-01

    Benign lymphoepithelial cyst (BLC) of the salivary gland is uncommon. Among report of these lesions, there were no previous cases of lymphoepithelial lesion (LeL) in human immunodeficiency virus type-1 (HIV-1) unrelated BLC. This study reports 3 cases of HIV-unrelated BLC containing LeL-like structures. Pathologically, 3 lesions were characterized by cuboidal epithelial-lined, cystic spaces, numerous lymphoid follicles, and dense lymphoplasmacytoid infiltrate. Moreover, small lymphocytes invaded the epithelial clusters forming LeL-like structures. Histological findings of 3 lesions resembled marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. However, staining with CD3, CD5, and CD20 demonstrated the mixed nature of small lymphocytes invading the epithelial clusters (LeLlike structures). Moreover, there were no CD43+ B-lymphocytes in any of the cases. The polytypic nature of B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. The 3 cases indicate that HIV-unrelated BLC should be added to the differential diagnosis of MALT-type lymphoma involving the parotid glands.

  10. Electrically conductive ceramic powders

    NASA Astrophysics Data System (ADS)

    Lu, Yanxia

    1999-11-01

    Electrically conductive ceramic powders were investigated in this project. There are three ways to produce those materials. The first is doping alkali metal into the titanium dioxides in an inert or reducing atmosphere. The second is reducing un-doped titanium dioxide, forming a non-stoichiometric composition in a hydrogen atmosphere. The third is to coat a conductive layer, reduced titanium dioxide, on an insulating core such as alumina. Highly conductive powders have been produced by all these processes. The conductivity of powder compacts ranged between 10-2 and 10° S/cm. A novel doping process was developed. All samples were doped by a solid-vapor reaction instead of a solid state reaction. Titanium dioxide was doped with alkali metals such as Na or Li in this study. The alkali metal atom contributes an electron to the host material (TiO2), which then creates Ti 3+ ion. The conductivity was enhanced by creating the donor level due to the presence of these Ti3+ ions. The conductivity of those alkali doped titanium oxides was dependent on the doping level and charge mobility. Non-stoichiometric titanium oxides were produced by reduction of titanium dioxide in a hydrogen atmosphere at 800°C to 1000°C for 2 to 6 hours. The reduced titanium oxides showed better stability with respect to conductivity at ambient condition when compared with the Na or Li doped samples. Conductive coatings were prepared by coating titanium precursors on insulating core materials like SiO2, Al2O3 or mica. The titania coating was made by hydrolysis of titanyl sulfate (TiOSO 4) followed by a reduction procedure to form reduced titanium oxide. The reduced titanium oxides are highly conductive. A uniform coating of titanium oxides on alumina cores was successfully produced. The conductivity of coated powder composites was a function of coating quantity and hydrolysis reaction temperature. The conductivity of the powder as a function of structure, composition, temperature, frequency and

  11. Polymers that Conduct Electricity.

    ERIC Educational Resources Information Center

    Edelson, Edward

    1983-01-01

    Although polymers are regarded as electrical insulators, it was discovered that they can be made to conduct electricity. This discovery has opened vast new practical and theoretical areas for exploration by physicists and chemists. Research studies with these conducting polymers and charge-transfer salts as well as possible applications are…

  12. Conductive Critical Thinking

    ERIC Educational Resources Information Center

    Paetkau, Mark

    2007-01-01

    One of my goals as an instructor is to teach students critical thinking skills. This paper presents an example of a student-led discussion of heat conduction at the first-year level. Heat loss from a human head is calculated using conduction and radiation models. The results of these plausible (but wrong) models of heat transfer contradict what…

  13. Thermal conductivity of comets

    NASA Technical Reports Server (NTRS)

    Vachon, R. I.; Kumar, G. N.; Khader, M. S.

    1974-01-01

    A value is described for the thermal conductivity of the frost layer and for the water-ice solid debris mixture. The value of the porous structure is discussed as a function of depth only. Graphs show thermal conductivity as a function of depth and temperature at constant porosity and density.

  14. Electrically conductive diamond electrodes

    DOEpatents

    Swain, Greg; Fischer, Anne ,; Bennett, Jason; Lowe, Michael

    2009-05-19

    An electrically conductive diamond electrode and process for preparation thereof is described. The electrode comprises diamond particles coated with electrically conductive doped diamond preferably by chemical vapor deposition which are held together with a binder. The electrodes are useful for oxidation reduction in gas, such as hydrogen generation by electrolysis.

  15. Conductive Education Evaluated.

    ERIC Educational Resources Information Center

    Stukat, Karl Gustav

    1995-01-01

    This paper evaluates two research projects concerned with conductive education for children with cerebral palsy, one in Germany and the other in the United Kingdom. Issues of generalizability and drawing causal conclusions are raised. The paper finds that neither the most sanguine expectations nor the worst misgivings about conductive education…

  16. Conductivity of disordered polycrystals

    NASA Astrophysics Data System (ADS)

    Chinh, Pham Duc

    1996-08-01

    New upper and lower bounds are constructed for the macroscopic conductivity of polycrystals with random microstructure, given the principal conductivities of the constituent crystals (and the volume fractions of phases in case of a multiphase polycrystal). The new bounds lie inside the well-known Hashin-Shtrikman ones.

  17. Death, attractiveness, moral conduct, and attitudes to public figures.

    PubMed

    North, Adrian C; Sheridan, Lorraine P

    In this study, 2,894 participants rated attitudes toward their favorite public figure on the Celebrity Attitude Scale. It was noted whether each figure was alive or dead, and a panel of four independent judges assessed each in terms of their moral conduct and physical attractiveness. Dead figures appealed less and were subject to lower "intense personal" celebrity worship, and death was unrelated to "borderline pathological" and "deleterious imitation" celebrity worship. Physical attractiveness was positively related to overall celebrity worship and "intense personal" celebrity worship, but negatively related to "borderline pathological" and "deleterious imitation" celebrity worship. Moral conduct was associated negatively with "deleterious imitation" celebrity worship. Results are discussed briefly in terms of their implications for research on physical attractiveness and "copycat suicide". PMID:20397615

  18. Optical Conductivity of Topological Surface States with Emergent Supersymmetry

    NASA Astrophysics Data System (ADS)

    Witczak-Krempa, William; Maciejko, Joseph

    2016-03-01

    Topological states of electrons present new avenues to explore the rich phenomenology of correlated quantum matter. Topological insulators (TIs) in particular offer an experimental setting to study novel quantum critical points (QCPs) of massless Dirac fermions, which exist on the sample's surface. Here, we obtain exact results for the zero- and finite-temperature optical conductivity at the semimetal-superconductor QCP for these topological surface states. This strongly interacting QCP is described by a scale invariant theory with emergent supersymmetry, which is a unique symmetry mixing bosons and fermions. We show that supersymmetry implies exact relations between the optical conductivity and two otherwise unrelated properties: the shear viscosity and the entanglement entropy. We discuss experimental considerations for the observation of these signatures in TIs.

  19. Death, attractiveness, moral conduct, and attitudes to public figures.

    PubMed

    North, Adrian C; Sheridan, Lorraine P

    In this study, 2,894 participants rated attitudes toward their favorite public figure on the Celebrity Attitude Scale. It was noted whether each figure was alive or dead, and a panel of four independent judges assessed each in terms of their moral conduct and physical attractiveness. Dead figures appealed less and were subject to lower "intense personal" celebrity worship, and death was unrelated to "borderline pathological" and "deleterious imitation" celebrity worship. Physical attractiveness was positively related to overall celebrity worship and "intense personal" celebrity worship, but negatively related to "borderline pathological" and "deleterious imitation" celebrity worship. Moral conduct was associated negatively with "deleterious imitation" celebrity worship. Results are discussed briefly in terms of their implications for research on physical attractiveness and "copycat suicide".

  20. Conductive fabric seal

    SciTech Connect

    Livesay, Ronald Jason; Mason, Brandon William; Kuhn, Michael Joseph; Rowe, Nathan Carl

    2015-10-13

    Disclosed are several examples of a system and method for detecting if an article is being tampered with. Included is a covering made of a substrate that is coated with a layer of an electrically conductive material that forms an electrically conductive surface having an electrical resistance. The covering is configured to at least partially encapsulate the article such that the article cannot be tampered with, without modifying the electrical resistance of the electrically conductive surface of the covering. A sensing device is affixed to the electrically conductive surface of the covering and the sensing device monitors the condition of the covering by producing a signal that is indicative of the electrical resistance of the electrically conductive surface of the covering. A measured electrical resistance that differs from a nominal electrical resistance is indicative of a covering that is being tampered with and an alert is communicated to an observer.

  1. Teaching Vocabulary to Turkish Young Learners in Semantically Related and Semantically Unrelated Sets by Using Digital Storytelling

    ERIC Educational Resources Information Center

    Aitkuzhinova-Arslan, Ainur; Gün, Süleyman; Üstünel, Eda

    2016-01-01

    Teaching vocabulary is a comprehensive process in foreign language learning requiring specific techniques of appropriate instruction and accurate strategy. The present study was conducted to examine the effects of teaching vocabulary to Turkish young learners in a semantic clustering way through digital storytelling. To investigate this aim, six…

  2. Trainees' Perceived Knowledge Gain Unrelated to the Training Domain: The Joint Action of Impression Management and Motives

    ERIC Educational Resources Information Center

    Chiaburu, Dan S.; Huang, Jason L.; Hutchins, Holly M.; Gardner, Richard G.

    2014-01-01

    Trainees' knowledge gains represent an important outcome in human resource development. In this research, we tested a model examining the joint influence of social desirability (impression management, self-deception) and motives (need for power, need for approval) on trainees' self-reported knowledge gain. We conducted a study with…

  3. Nerve conduction velocity

    MedlinePlus

    ... to measure the speed of the nerve signals. Electromyography (recording from needles placed into the muscles) is ... Often, the nerve conduction test is followed by electromyography (EMG). In this test, needles are placed into ...

  4. Conductive open frameworks

    DOEpatents

    Yaghi, Omar M.; Wan, Shun; Doonan, Christian J.; Wang, Bo; Deng, Hexiang

    2016-02-23

    The disclosure relates generally to materials that comprise conductive covalent organic frameworks. The disclosure also relates to materials that are useful to store and separate gas molecules and sensors.

  5. Electrically conductive material

    DOEpatents

    Singh, J.P.; Bosak, A.L.; McPheeters, C.C.; Dees, D.W.

    1993-09-07

    An electrically conductive material is described for use in solid oxide fuel cells, electrochemical sensors for combustion exhaust, and various other applications possesses increased fracture toughness over available materials, while affording the same electrical conductivity. One embodiment of the sintered electrically conductive material consists essentially of cubic ZrO[sub 2] as a matrix and 6-19 wt. % monoclinic ZrO[sub 2] formed from particles having an average size equal to or greater than about 0.23 microns. Another embodiment of the electrically conductive material consists essentially at cubic ZrO[sub 2] as a matrix and 10-30 wt. % partially stabilized zirconia (PSZ) formed from particles having an average size of approximately 3 microns. 8 figures.

  6. Electrically conductive material

    DOEpatents

    Singh, Jitendra P.; Bosak, Andrea L.; McPheeters, Charles C.; Dees, Dennis W.

    1993-01-01

    An electrically conductive material for use in solid oxide fuel cells, electrochemical sensors for combustion exhaust, and various other applications possesses increased fracture toughness over available materials, while affording the same electrical conductivity. One embodiment of the sintered electrically conductive material consists essentially of cubic ZrO.sub.2 as a matrix and 6-19 wt. % monoclinic ZrO.sub.2 formed from particles having an average size equal to or greater than about 0.23 microns. Another embodiment of the electrically conductive material consists essentially at cubic ZrO.sub.2 as a matrix and 10-30 wt. % partially stabilized zirconia (PSZ) formed from particles having an average size of approximately 3 microns.

  7. Solution Conductivity Apparatus.

    ERIC Educational Resources Information Center

    Haworth, Daniel T.; Bartelt, Mark R.; Kenney, Michael J.

    1999-01-01

    Describes the construction of a conductivity meter that includes a timer and a readout display that provides semiquantitative information. The meter can be made into a hand-held or lecture hall (demonstration) version. (WRM)

  8. Proton conducting cerate ceramics

    SciTech Connect

    Coffey, G.W.; Pederson, L.R.; Armstrong, T.R.; Bates, J.L.; Weber, W.J.

    1995-08-01

    Cerate perovskites of the general formula AM{sub x}Ce{sub 1-x}O{sub 3-{delta}}, where A = Sr or Ba and where M = Gd, Nd, Y, Yb or other rare earth dopant, are known to conduct a protonic current. Such materials may be useful as the electrolyte in a solid oxide fuel cell operating at intermediate temperatures, as an electrochemical hydrogen separation membrane, or as a hydrogen sensor. Conduction mechanisms in these materials were evaluated using dc cyclic voltammetry and mass spectrometry, allowing currents and activation energies for proton, electron, and oxygen ion contributions to the total current to be determined. For SrYb{sub 0.05}Ce{sub 0.95}O{sub 3-{delta}}, one of the best and most environmentally stable compositions, proton conduction followed two different mechanisms: a low temperature process, characterized by an activation energy of 0.42{+-}0.04 eV, and a high temperature process, characterized by an activation energy of 1.38{+-}0.13 eV. It is believed that the low temperature process is dominated by grain boundary conduction while bulk conduction is responsible for the high temperature process. The activation energy for oxygen ion conduction (0.97{+-}0.10 eV) agrees well with other oxygen conductors, while that for electronic conduction, 0.90{+-}0.09 eV, is affected by a temperature-dependent electron carrier concentration. Evaluated by direct measurement of mass flux through a dense ceramic with an applied dc field, oxygen ions were determined to be the majority charge carrier except at the lowest temperatures, followed by electrons and then protons.

  9. Cartilage conduction hearing.

    PubMed

    Shimokura, Ryota; Hosoi, Hiroshi; Nishimura, Tadashi; Yamanaka, Toshiaki; Levitt, Harry

    2014-04-01

    Sound information is known to travel to the cochlea via either air or bone conduction. However, a vibration signal, delivered to the aural cartilage via a transducer, can also produce a clearly audible sound. This type of conduction has been termed "cartilage conduction." The aural cartilage forms the outer ear and is distributed around the exterior half of the external auditory canal. In cartilage conduction, the cartilage and transducer play the roles of a diaphragm and voice coil of a loudspeaker, respectively. There is a large gap between the impedances of cartilage and skull bone, such that cartilage vibrations are not easily transmitted through bone. Thus, these methods of conduction are distinct. In this study, force was used to apply a transducer to aural cartilage, and it was found that the sound in the auditory canal was amplified, especially for frequencies below 2 kHz. This effect was most pronounced at an application force of 1 N, which is low enough to ensure comfort in the design of hearing aids. The possibility of using force adjustments to vary amplification may also have applications for cell phone design.

  10. Proliferating conduction by isomerism

    NASA Astrophysics Data System (ADS)

    Kaur, Rupan Preet; Sawhney, Ravinder Singh; Engles, Derick

    2015-01-01

    The electrical conduction of isomers of anthracene molecule attached between two semi-infinite gold electrodes was simulated using extended Huckel theory (EHT)-based on semi-empirical model in this research work. The electron transport parameters were examined in two epochs by buffering anthracene and its isomer phenanthrene alternatively between gold electrodes using sulphur as an alligator clip, under variegated bias voltages. Differential NDR effect was observed in both the cases but phenanthrene exhibited more linear I-V curve than its counterpart, anthracene. The simulated results discovered phenanthrene as a better candidate than anthracene towards contributing to electrical conduction in molecular junctions. Phenanthrene reported maximum conductance of 0.74G0 whereas anthracene exhibited 0.03G0 at 0.8V.

  11. Age Effects and Temporal Trends in HPV-Related and HPV-Unrelated Oral Cancer in the United States: A Multistage Carcinogenesis Modeling Analysis.

    PubMed

    Brouwer, Andrew F; Eisenberg, Marisa C; Meza, Rafael

    2016-01-01

    Differences in prognosis in HPV-positive and HPV-negative oral (oropharyngeal and oral cavity) squamous cell carcinomas (OSCCs) and increasing incidence of HPV-related cancers have spurred interest in demographic and temporal trends in OSCC incidence. We leverage multistage clonal expansion (MSCE) models coupled with age-period-cohort (APC) epidemiological models to analyze OSCC data in the SEER cancer registry (1973-2012). MSCE models are based on the initiation-promotion-malignant conversion paradigm in carcinogenesis and allow for interpretation of trends in terms of biological mechanisms. APC models seek to differentiate between the temporal effects of age, period, and birth cohort on cancer risk. Previous studies have looked at the effect of period and cohort on tumor initiation, and we extend this to compare model fits of period and cohort effects on each of tumor initiation, promotion, and malignant conversion rates. HPV-related, HPV-unrelated except oral tongue, and HPV-unrelated oral tongue sites are best described by placing period and cohort effects on the initiation rate. HPV-related and non-oral-tongue HPV-unrelated cancers have similar promotion rates, suggesting similar tumorigenesis dynamics once initiated. Estimates of promotion rates at oral tongue sites are lower, corresponding to a longer sojourn time; this finding is consistent with the hypothesis of an etiology distinct from HPV or alcohol and tobacco use. Finally, for the three subsite groups, men have higher initiation rates than women of the same race, and black people have higher promotion than white people of the same sex. These differences explain part of the racial and sex differences in OSCC incidence.

  12. Contribution of HLA-A/B/C/DRB1/DQB1 common haplotypes to donor search outcome in unrelated hematopoietic stem cell transplantation.

    PubMed

    Pédron, Béatrice; Guérin-El Khourouj, Valérie; Dalle, Jean-Hugues; Ouachée-Chardin, Marie; Yakouben, Karima; Corroyez, France; Auvrignon, Anne; Petit, Arnaud; Landman-Parker, Judith; Leverger, Guy; Baruchel, André; Sterkers, Ghislaine

    2011-11-01

    In unrelated hematopoietic stem cell transplantation (HSCT), the prediction of donor search outcome at the time of search initiation is of great value for the physicians to delineate the strategy of patient care. The probability of finding an unrelated donor is high for patients who carry at least 1 of the 10 most common HLA haplotypes in Caucasians. As only 10% to 20% patients respond to this criterion, here we aimed at finding additional common haplotypes to improve the prediction of a successful search. HLA broad HLA-A/B/DRB1 haplotypes that were observed with frequencies ≥0.19% in patient families of European origin and that split into ≤2 predominant 4-digit HLA-A/B/C/DRB1/DQB1 haplotypes were considered as common. Carriage of at least 1 of those in 168 patients of various geographic areas with no family donor was confronted to the chance of finding ≥9/10 HLA-matched unrelated donors. Fifty common 4-digit haplotypes were identified. A higher (P < 5 × 10(-6)) chance of finding a suitable donor was found for 55 of 170 (32%) recipients that carried at least 1 of these common haplotypes. Up to now, estimates classified patients into ≥3 groups of probability with ≥1 intermediate group of poor utility for the clinicians. Considering carriage of these common haplotypes together with the frequencies of alleles and of B/C and DRB1/DQB1 associations, which are carried by patient HLA haplotypes, we could classify the patients into 2 groups of probability with a 98% and 26% chance of finding a donor, respectively. Prediction of search outcome could be improved by including the 50 most common HLA haplotypes in the current approaches.

  13. Age Effects and Temporal Trends in HPV-Related and HPV-Unrelated Oral Cancer in the United States: A Multistage Carcinogenesis Modeling Analysis.

    PubMed

    Brouwer, Andrew F; Eisenberg, Marisa C; Meza, Rafael

    2016-01-01

    Differences in prognosis in HPV-positive and HPV-negative oral (oropharyngeal and oral cavity) squamous cell carcinomas (OSCCs) and increasing incidence of HPV-related cancers have spurred interest in demographic and temporal trends in OSCC incidence. We leverage multistage clonal expansion (MSCE) models coupled with age-period-cohort (APC) epidemiological models to analyze OSCC data in the SEER cancer registry (1973-2012). MSCE models are based on the initiation-promotion-malignant conversion paradigm in carcinogenesis and allow for interpretation of trends in terms of biological mechanisms. APC models seek to differentiate between the temporal effects of age, period, and birth cohort on cancer risk. Previous studies have looked at the effect of period and cohort on tumor initiation, and we extend this to compare model fits of period and cohort effects on each of tumor initiation, promotion, and malignant conversion rates. HPV-related, HPV-unrelated except oral tongue, and HPV-unrelated oral tongue sites are best described by placing period and cohort effects on the initiation rate. HPV-related and non-oral-tongue HPV-unrelated cancers have similar promotion rates, suggesting similar tumorigenesis dynamics once initiated. Estimates of promotion rates at oral tongue sites are lower, corresponding to a longer sojourn time; this finding is consistent with the hypothesis of an etiology distinct from HPV or alcohol and tobacco use. Finally, for the three subsite groups, men have higher initiation rates than women of the same race, and black people have higher promotion than white people of the same sex. These differences explain part of the racial and sex differences in OSCC incidence. PMID:26963717

  14. Age Effects and Temporal Trends in HPV-Related and HPV-Unrelated Oral Cancer in the United States: A Multistage Carcinogenesis Modeling Analysis

    PubMed Central

    Brouwer, Andrew F.; Eisenberg, Marisa C.; Meza, Rafael

    2016-01-01

    Differences in prognosis in HPV-positive and HPV-negative oral (oropharyngeal and oral cavity) squamous cell carcinomas (OSCCs) and increasing incidence of HPV-related cancers have spurred interest in demographic and temporal trends in OSCC incidence. We leverage multistage clonal expansion (MSCE) models coupled with age—period—cohort (APC) epidemiological models to analyze OSCC data in the SEER cancer registry (1973–2012). MSCE models are based on the initiation—promotion—malignant conversion paradigm in carcinogenesis and allow for interpretation of trends in terms of biological mechanisms. APC models seek to differentiate between the temporal effects of age, period, and birth cohort on cancer risk. Previous studies have looked at the effect of period and cohort on tumor initiation, and we extend this to compare model fits of period and cohort effects on each of tumor initiation, promotion, and malignant conversion rates. HPV-related, HPV-unrelated except oral tongue, and HPV-unrelated oral tongue sites are best described by placing period and cohort effects on the initiation rate. HPV-related and non-oral-tongue HPV-unrelated cancers have similar promotion rates, suggesting similar tumorigenesis dynamics once initiated. Estimates of promotion rates at oral tongue sites are lower, corresponding to a longer sojourn time; this finding is consistent with the hypothesis of an etiology distinct from HPV or alcohol and tobacco use. Finally, for the three subsite groups, men have higher initiation rates than women of the same race, and black people have higher promotion than white people of the same sex. These differences explain part of the racial and sex differences in OSCC incidence. PMID:26963717

  15. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

    PubMed

    Konuma, Takaaki; Tsukada, Nobuhiro; Kanda, Junya; Uchida, Naoyuki; Ohno, Yuju; Miyakoshi, Shigesaburo; Kanamori, Heiwa; Hidaka, Michihiro; Sakura, Toru; Onizuka, Makoto; Kobayashi, Naoki; Sawa, Masashi; Eto, Tetsuya; Matsuhashi, Yoshiko; Kato, Koji; Ichinohe, Tatsuo; Atsuta, Yoshiko; Miyamura, Koichi

    2016-05-01

    Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.

  16. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

    PubMed

    Konuma, Takaaki; Tsukada, Nobuhiro; Kanda, Junya; Uchida, Naoyuki; Ohno, Yuju; Miyakoshi, Shigesaburo; Kanamori, Heiwa; Hidaka, Michihiro; Sakura, Toru; Onizuka, Makoto; Kobayashi, Naoki; Sawa, Masashi; Eto, Tetsuya; Matsuhashi, Yoshiko; Kato, Koji; Ichinohe, Tatsuo; Atsuta, Yoshiko; Miyamura, Koichi

    2016-05-01

    Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT. PMID:26910296

  17. Electrical Conductivity in Textiles

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Copper is the most widely used electrical conductor. Like most metals, though, it has several drawbacks: it is heavy, expensive, and can break. Fibers that conduct electricity could be the solutions to these problems, and they are of great interest to NASA. Conductive fibers provide lightweight alternatives to heavy copper wiring in a variety of settings, including aerospace, where weight is always a chief concern. This is an area where NASA is always seeking improved materials. The fibers are also more cost-effective than metals. Expenditure is another area where NASA is always looking to make improvements. In the case of electronics that are confined to small spaces and subject to severe stress, copper is prone to breaking and losing connection over time. Flexible conductive fibers eliminate that problem. They are more supple and stronger than brittle copper and, thus, find good use in these and similar situations. While clearly a much-needed material, electrically conductive fibers are not readily available. The cost of new technology development, with all the pitfalls of troubleshooting production and the years of testing, and without the guarantee of an immediate market, is often too much of a financial hazard for companies to risk. NASA, however, saw the need for electrical fibers in its many projects and sought out a high-tech textile company that was already experimenting in this field, Syscom Technology, Inc., of Columbus, Ohio. Syscom was founded in 1993 to provide computer software engineering services and basic materials research in the areas of high-performance polymer fibers and films. In 1999, Syscom decided to focus its business and technical efforts on development of high-strength, high-performance, and electrically conductive polymer fibers. The company developed AmberStrand, an electrically conductive, low-weight, strong-yet-flexible hybrid metal-polymer YARN.

  18. Transparent Conductive Nanostructures

    SciTech Connect

    2008-06-22

    The objectives of this program between UT-Battelle, LLC (the ''Contractor'') and (Battelle Memorial Institute) (the "Participant") were directed towards achieving significant improvement: in the electrical conductivity and optical/infrared transmission of single-wall carbon nanotube (SWNT)-based composite materials. These materials will be used in coating applications that range from aircraft canopies to display applications. The goal of the project was to obtain supported mats of SWNTs with sheet conductivities approaching 10 ohms/square combined with high optical transmission (>85% transmission at 550 nm), thereby permitting their application as a replacement for indium tin oxide (ITO) in a variety of applications such as flexible displays.

  19. Conducting hybrid polymeric systems

    SciTech Connect

    Aldissi, M.; White, J.W.; Agnew, S.; Jorgensen, B.S.

    1987-09-01

    The studies took advantage of the opportunities offered by copolymerization for gaining insight into electrical conduction, morphology, phase separation, polymer-polymer interfaces, and solubility. Copolymerization is technologically important for it allows one to tailor-make products with specifically desired properties. However, the utility of copolymerization involving conjugated, rigid components could be different from that of conventional polymers. This paper is focused on the synthesis and properties of various materials: Rod-coil systems such as polyisoprene/polyacetylene diblock copolymers (resonance raman and small angle neutron scattering studies correlated to conductivity); and alternating copolymers such as poly (arylpyrroles) (electrochemical synthesis and characterization). 8 refs., 4 figs.

  20. Use of Matched Unrelated Donors Compared with Matched Related Donors is Associated with Lower Relapse and Superior Progression Free Survival after Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation

    PubMed Central

    Ho, Vincent T.; Kim, Haesook T.; Aldridge, Julie; Liney, Deborah; Kao, Grace; Armand, Philippe; Koreth, John; Cutler, Corey; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Alyea, Edwin P.

    2011-01-01

    As success of reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes. To assess whether use of unrelated donors (URD) engenders more potent GVL in RIC HSCT compared to matched related donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA matched URD (n= 246) and MRD (n=187) RIC HSCT for hematologic malignancies at our institution. Diseases included: AML(127), NHL(71), CLL (68), MDS (64), HD(40), CML (25), MM(23), MPD (12), ALL(7), other leukemia (1). All received uniform fludarabine and intravenous busulfan conditioning, and GVHD prophylaxis with tacrolimus/mini-MTX or tacrolimus/sirolimus +/− mini-MTX. Unrelated donors were younger compared to MRD (median age: 33 yrs vs. 52 yrs, p<0.0001), and provided larger CD34+ products (median CD34+ cells infused: 8.7 × 106/kg vs. 7.5 × 106/kg, p=0.002). Distribution of diseases, disease risk, prior transplant, and CMV status was similar in both cohorts. Cumulative incidence of grade II–IV acute GVHD (at day+180), 2 year-chronic GVHD, and 2-year non-relapse mortality (NRM) were 20% vs. 16%, 55% vs. 50%, and 8% vs. 6% in URD and MRD, respectively (p=NS). Cumulative incidence of relapse at 2 years was lower in URD, 52% vs. 65% (p=0.005). With median follow-up of 26.5 and 35.8 months, 2-yr progression free survival (PFS) was significantly better in unrelated donor transplants, 39.5% for URD and 29% for MRD (p= 0.01). Overall survival at 2 years were 56% for URD vs. 50% for MRD (p=0.53). In multivariable analysis, URD was associated with a lower risk of relapse (HR 0.67, p =0.002) and superior PFS (HR 0.69, p=0.002). These results suggest that URD is associated with greater GVL activity than MRD, and could have practice changing impact on future donor selection in RIC HSCT. PMID:21193054

  1. Conducting Educational Design Research

    ERIC Educational Resources Information Center

    McKenney, Susan; Reeves, Thomas

    2012-01-01

    Educational design research blends scientific investigation with systematic development and implementation of solutions to educational problems. Empirical investigation is conducted in real learning settings--not laboratories--to craft usable and effective solutions. At the same time, the research is carefully structured to produce theoretical…

  2. Thermal conductivity of metals

    NASA Technical Reports Server (NTRS)

    Kazem, Sayyed M.

    1990-01-01

    The objective is to familiarize students with steady and unsteady heat transfer by conduction and with the effect of thermal conductivity upon temperature distribution through a homogeneous substance. The elementary heat conduction experiment presented is designed for associate degree technology students in a simple manner to enhance their intuition and to clarify many confusing concepts such as temperature, thermal energy, thermal conductivity, heat, transient and steady flows. The equipment set is safe, small, portable (10 kg) and relatively cheap (about $1200): the electric hot plate 2 kg (4.4 lb) for $175: the 24 channel selector and Thermocouple Digital Readout (Trendicator) 4.5 kg (10 lb) for about $1000; the three metal specimens (each of 2.5 cm diameter and 11 cm length), base plate and the bucket all about 3 kg (7 lb) for about $25. The experiment may take from 60 to 70 minutes. Although the hot plate surface temperature could be set from 90 to 370 C (maximum of 750 watts) it is a good practice to work with temperatures of 180 to 200 C (about 400 watts). They may experiment in squads of 2, 3 or even 4, or the instructor may demonstrate it for the whole class.

  3. Soft, thermally conductive material

    NASA Technical Reports Server (NTRS)

    Anderson, A. J.

    1974-01-01

    Silicon rubber filled with high percentage of silver-plated copper microspheres provides soft, thermally conductive seat for thermal switch. Material also could be used in thin sheet form to prevent corrosion between dissimilar metals while maintaining good thermal communication. It could be used as thermal gasketing.

  4. Conducting Telephone Conference IEPs

    ERIC Educational Resources Information Center

    Patterson, Philip Patrick; Petit, Constance; Williams, Shandelyn

    2007-01-01

    Synchronizing the availability of team members for Individual Education Plan (IEP) meetings can be a daunting task. Fortunately, the Individuals with Disabilities Education Improvement Act of 2004 permits alternative means of conducting such meetings. An example of an alternate means is a telephone conference, whereby parents communicate over the…

  5. Lithium ion conducting electrolytes

    DOEpatents

    Angell, Charles Austen; Liu, Changle; Xu, Kang; Skotheim, Terje A.

    1999-01-01

    The present invention relates generally to highly conductive alkali-metal ion non-crystalline electrolyte systems, and more particularly to novel and unique molten (liquid), rubbery, and solid electrolyte systems which are especially well suited for use with high current density electrolytic cells such as primary and secondary batteries.

  6. Conductance Steamflow relationship

    SciTech Connect

    Whitney Trainor-Guitton

    2015-04-01

    These histograms represent our calibration of conductance of a volcanic geothermal field (with a clay cap) and the observed steam flow rates. See the following paper for further description: Trainor-Guitton, Hoversten,Nordquist, Intani, Value of information analysis using geothermal field data: accounting for multiple interpretations & determining new drilling locations. SEG Abstracts 2015.

  7. Conducting the Heat

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Heat conduction plays an important role in the efficiency and life span of electronic components. To keep electronic components running efficiently and at a proper temperature, thermal management systems transfer heat generated from the components to thermal surfaces such as heat sinks, heat pipes, radiators, or heat spreaders. Thermal surfaces absorb the heat from the electrical components and dissipate it into the environment, preventing overheating. To ensure the best contact between electrical components and thermal surfaces, thermal interface materials are applied. In addition to having high conductivity, ideal thermal interface materials should be compliant to conform to the components, increasing the surface contact. While many different types of interface materials exist for varying purposes, Energy Science Laboratories, Inc. (ESLI), of San Diego, California, proposed using carbon velvets as thermal interface materials for general aerospace and electronics applications. NASA s Johnson Space Center granted ESLI a Small Business Innovation Research (SBIR) contract to develop thermal interface materials that are lightweight and compliant, and demonstrate high thermal conductance even for nonflat surfaces. Through Phase II SBIR work, ESLI created Vel-Therm for the commercial market. Vel-Therm is a soft, carbon fiber velvet consisting of numerous high thermal conductivity carbon fibers anchored in a thin layer of adhesive. The velvets are fabricated by precision cutting continuous carbon fiber tows and electrostatically flocking the fibers into uncured adhesive, using proprietary techniques.

  8. Low electrolytic conductivity standards

    SciTech Connect

    Wu, Y.C.; Berezansky, P.A.

    1995-09-01

    The monitoring and control of the quality of feedwater and boiler water are necessary for power plants. The generation of steam at high temperature and pressure requires that contaminants be strictly limited to very low levels to prevent corrosion and scaling. Standards of low electrolytic conductivity were developed to satisfy the demands of the US Navy and American industry for the measurement of high quality water. The criteria for the selection of appropriate solvent and solutes, based on the principles of equivalent conductivity and Onsager`s limiting law, are described. Dilute solutions of potassium chloride and benzoic acid in 30% n-propanol-water have been chosen as standards. The electrolytic conductivity of both sets of these solutions as a function of molality was determined. Solutions of potassium chloride and of benzoic acid are recommended for use as 5, 10, 15, 20, and 25 {micro}S/cm conductivity standards. Solutions prepared from potassium chloride in 30% n-propanol-water have been certified as Standard Reference Materials (SRMs). SRM 3198 and SRM 3199 are certified nominally at 5 and 15 {micro}S/cm, respectively, at 25.000 C.

  9. Benefits of Conducting Research.

    ERIC Educational Resources Information Center

    Anderson, Frances E.

    2001-01-01

    Metaphors for researchers, such as a crusader; a traveler; an explorer; a miner; an astronaut; a biblical Daniel; a Samurai; and an archaeologist are discussed. Benefits of conducting research are enumerated, including building the knowledge base for art therapy; increasing professional opportunities; improving client care; and advancing the…

  10. Lithium ion conducting electrolytes

    DOEpatents

    Angell, C. Austen; Liu, Changle

    1996-01-01

    A liquid, predominantly lithium-conducting, ionic electrolyte having exceptionally high conductivity at temperatures of 100.degree. C. or lower, including room temperature, and comprising the lithium salts selected from the group consisting of the thiocyanate, iodide, bromide, chloride, perchlorate, acetate, tetrafluoroborate, perfluoromethane sulfonate, perfluoromethane sulfonamide, tetrahaloaluminate, and heptahaloaluminate salts of lithium, with or without a magnesium-salt selected from the group consisting of the perchlorate and acetate salts of magnesium. Certain of the latter embodiments may also contain molecular additives from the group of acetonitrile (CH.sub.3 CN) succinnonitrile (CH.sub.2 CN).sub.2, and tetraglyme (CH.sub.3 --O--CH.sub.2 --CH.sub.2 --O--).sub.2 (or like solvents) solvated to a Mg.sup.+2 cation to lower the freezing point of the electrolyte below room temperature. Other particularly useful embodiments contain up to about 40, but preferably not more than about 25, mol percent of a long chain polyether polymer dissolved in the lithium salts to provide an elastic or rubbery solid electrolyte of high ambient temperature conductivity and exceptional 100.degree. C. conductivity. Another embodiment contains up to about but not more than 10 mol percent of a molecular solvent such as acetone.

  11. Lithium ion conducting electrolytes

    DOEpatents

    Angell, C.A.; Liu, C.

    1996-04-09

    A liquid, predominantly lithium-conducting, ionic electrolyte is described having exceptionally high conductivity at temperatures of 100 C or lower, including room temperature, and comprising the lithium salts selected from the group consisting of the thiocyanate, iodide, bromide, chloride, perchlorate, acetate, tetrafluoroborate, perfluoromethane sulfonate, perfluoromethane sulfonamide, tetrahaloaluminate, and heptahaloaluminate salts of lithium, with or without a magnesium-salt selected from the group consisting of the perchlorate and acetate salts of magnesium. Certain of the latter embodiments may also contain molecular additives from the group of acetonitrile (CH{sub 3}CN), succinnonitrile (CH{sub 2}CN){sub 2}, and tetraglyme (CH{sub 3}--O--CH{sub 2}--CH{sub 2}--O--){sub 2} (or like solvents) solvated to a Mg{sup +2} cation to lower the freezing point of the electrolyte below room temperature. Other particularly useful embodiments contain up to about 40, but preferably not more than about 25, mol percent of a long chain polyether polymer dissolved in the lithium salts to provide an elastic or rubbery solid electrolyte of high ambient temperature conductivity and exceptional 100 C conductivity. Another embodiment contains up to about but not more than 10 mol percent of a molecular solvent such as acetone. 2 figs.

  12. Central motor conduction time by magnetic stimulation of the cortex and peripheral nerve conduction follow-up studies in Friedreich's ataxia.

    PubMed

    Cruz-Martínez, A; Palau, F

    1997-12-01

    A follow-up clinical study, peripheral motor and sensory nerve conduction velocities and central motor conduction by magnetic stimulation of the cortex were performed in 13 patients with classical Friedreich's ataxia (FA) phenotype, for a period of 9-12 years. Clinical worsening was unrelated to peripheral nerve abnormalities. The amplitude of the nerve action potentials and delayed conduction velocity remained unchanged for several years. Central motor conduction times were abnormal in all patients. Clinical conditions worsened significantly between successive examinations with significant increments in threshold and significant decrement of the amplitude of motor evoked potentials. The results are consistent with progressive pyramidal and cerebellar pathways involvement as the cause of clinical worsening in FA.

  13. Inverse heat conduction problems

    NASA Astrophysics Data System (ADS)

    Orlande, Helcio Rangel Barreto

    We present the solution of the following inverse problems: (1) Inverse Problem of Estimating Interface Conductance Between Periodically Contacting Surfaces; (2) Inverse Problem of Estimating Interface Conductance During Solidification via Conjugate Gradient Method; (3) Determination of the Reaction Function in a Reaction-Diffusion Parabolic Problem; and (4) Simultaneous Estimation of Thermal Diffusivity and Relaxation Time with Hyperbolic Heat Conduction Model. Also, we present the solution of a direct problem entitled: Transient Thermal Constriction Resistance in a Finite Heat Flux Tube. The Conjugate Gradient Method with Adjoint Equation was used in chapters 1-3. The more general function estimation approach was treated in these chapters. In chapter 1, we solve the inverse problem of estimating the timewise variation of the interface conductance between periodically contacting solids, under quasi-steady-state conditions. The present method is found to be more accurate than the B-Spline approach for situations involving small periods, which are the most difficult on which to perform the inverse analysis. In chapter 2, we estimate the timewise variation of the interface conductance between casting and mold during the solidification of aluminum. The experimental apparatus used in this study is described. In chapter 3, we present the estimation of the reaction function in a one dimensional parabolic problem. A comparison of the present function estimation approach with the parameter estimation technique, wing B-Splines to approximate the reaction function, revealed that the use of function estimation reduces the computer time requirements. In chapter 4 we present a finite difference solution for the transient constriction resistance in a cylinder of finite length with a circular contact surface. A numerical grid generation scheme was used to concentrate grid points in the regions of high temperature gradients in order to reduce discretization errors. In chapter 6, we

  14. Nanostructured conductive polymeric materials

    NASA Astrophysics Data System (ADS)

    Al-Saleh, Mohammed H.

    Conductive polymer composites (CPCs) are a suitable alternative to metals in many applications due to their light-weight, corrosion resistance, low cost, ease of processing and design flexibility. CPCs have been formulated using different types of conductive fillers. In this PhD thesis, the focus is on CPCs for electrostatic discharge (ESD) protection and electromagnetic interference (EMI) attenuation. Despite the versatility of conductive fillers, carbon black (CB) has been the dominant filler to make CPCs for ESD protection applications because CB/polymer composites have a cost advantage over all other CPCs. For EMI shielding, stainless steel fibres and metal coated fibers are the preferred fillers, however CPCs made of those fibers are not the dominant EMI shielding materials. Metal coated and polymer plated polymers are the most widely used EMI shielding options. The limited use of CPCs in the EMI shielding market is because the high filler loading required to formulate a composite with an adequate level of shielding remarkably increases the composite price. In order to increase the competitiveness of CPCs, percolation threshold should be minimized as much as possible and composites with high EMI shielding capabilities at low filler loading should be formulated because all conductive fillers are expensive compared to polymers. In this thesis, two different methodologies to reduce percolation threshold in CPCs have been successfully developed and a CPC with exceptional EMI shielding capability has been formulated using copper nanowires as conductive filler. The first percolation threshold reduction technique is based on the selective localization of CB at the interface of immiscible polymer blend. The technique requires adding a copolymer that prefers the blend's interface and for which CB nanoparticles has the highest affinity. The second method is based on producing a CPC powder and then using this powder as a conductive filler to produce composite by dry

  15. Marrow grafts between phenotypically DLA-identical and haploidentical unrelated dogs: additional antigens controlling engraftment are not detected by cell-mediated lympholysis

    SciTech Connect

    Deeg, H.J.; Storb, R.; Raff, R.F.; Weiden, P.L.; DeRose, S.; Thomas, E.D.

    1982-01-01

    Bone marrow transplants with low marrow cell doses (less than or equal to4 X 10/sup 8/ cells/kg) from unrelated donors were carried out in 16 dogs conditioned with 9 Gy (900 rad) of total body irradiation. No immunosuppression was given after grafting. Eleven donor-recipient pairs were phenotypically identical (group 1) for the known antigens of the canine major histocompatibility complex (DLA) and in five the donor was homozygous and the recipient heterozygous for DLA (group 2), as determined by serological histocompatibility typing and mixed leukocyte cultures including homozygous cell typing. In addition, lymphocytes from donors and recipients in group 1 were mutually nonreactive in cell-mediated lympholysis; lymphocytes from recipients in group 2 were not cytotoxic against donor cells. Eight dogs rejected their grafts and eight showed sustained engraftment; of these, four died from graft-versus-host disease. The incidence of rejection was higher than in DLA-identical littermates but lower than in DLA-nonidentical unrelated or littermate dogs. These results indicate that antigens different from the recognized alleles at DLA are involved in the control of engraftment. These antigens most likely represent the expression of unrecognized differences within DLA or are coded for by a locus different from but linked to DLA-A, B, C or D; they are not recognized in the cell-mediated lympholysis assay.

  16. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing.

    PubMed

    Maris, Michael B; Sandmaier, Brenda M; Storer, Barry E; Maloney, David G; Shizuru, Judith A; Agura, Edward; Kliem, Constanze; Pulsipher, Michael; Maziarz, Richard T; McSweeney, Peter A; Wade, James; Langston, Amelia A; Chauncey, Thomas R; Bruno, Benedetto; Blume, Karl G; Storb, Rainer

    2006-04-01

    We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m(2), 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.

  17. Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

    PubMed

    Gagne, K; Loiseau, P; Dubois, V; Dufossé, F; Perrier, P; Dormoy, A; Jollet, I; Renac, V; Masson, D; Picard, C; Lafarge, X; Hanau, D; Quainon, F; Delbos, F; Coeffic, B; Absi, Léna; Eliaou, J-F; Moalic, V; Fort, M; de Matteis, M; Theodorou, I; Hau, F; Batho, A; Pedron, B; Caillat-Zucman, S; Marry, E; Raus, N; Yakoub-Agha, I; Cesbron, A

    2015-02-01

    We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

  18. Mycobacterium tuberculosis PstS1 amplifies IFN-γ and induces IL-17/IL-22 responses by unrelated memory CD4+ T cells via dendritic cell activation.

    PubMed

    Palma, Carla; Schiavoni, Giovanna; Abalsamo, Laura; Mattei, Fabrizio; Piccaro, Giovanni; Sanchez, Massimo; Fernandez, Carmen; Singh, Mahavir; Gabriele, Lucia

    2013-09-01

    The immunological mechanisms that modulate protection during Mycobacterium tuberculosis (Mtb) infection or vaccination are not fully understood. Secretion of IFN-γ and, to a lesser extent, of IL-17 by CD4(+) T cells plays a major role both in protection and immunopathology. Few Mtb Ags interacting with DCs affect priming, activation, and regulation of Ag-unrelated CD4(+) T-cell responses. Here we demonstrate that PstS1, a 38 kDa-lipoprotein of Mtb, promotes Ag-independent activation of memory T lymphocytes specific for Ag85B or Ag85A, two immunodominant protective Ags of Mtb. PstS1 expands CD4(+) and CD8(+) memory T cells, amplifies secretion of IFN-γ and IL-22 and induces IL-17 production by effector memory cells in an Ag-unrelated manner in vitro and in vivo. These effects were mediated through the stimulation of DCs, particularly of the CD8α(-) subtype, which respond to PstS1 by undergoing phenotypic maturation and by secreting IL-6, IL-1β and, to a lower extent, IL-23. IL-6 secretion by PstS1-stimulated DCs was required for IFN-γ, and to a lesser extent for IL-22 responses by Ag85B-specific memory T cells. These results may open new perspectives for immunotherapeutic strategies to control Th1/Th17 immune responses in Mtb infections and in vaccinations against tuberculosis. PMID:23719937

  19. Super ionic conductive glass

    DOEpatents

    Susman, Sherman; Volin, Kenneth J.

    1984-01-01

    An ionically conducting glass for use as a solid electrolyte in a power or secondary cell containing an alkali metal-containing anode and a cathode separated by an alkali metal ion conducting glass having an ionic transference number of unity and the general formula: A.sub.1+x D.sub.2-x/3 Si.sub.x P.sub.3-x O.sub.12-2x/3, wherein A is a network modifier for the glass and is an alkali metal of the anode, D is an intermediate for the glass and is selected from the class consisting of Zr, Ti, Ge, Al, Sb, Be, and Zn and X is in the range of from 2.25 to 3.0. Of the alkali metals, Na and Li are preferred and of the intermediate, Zr, Ti and Ge are preferred.

  20. Super ionic conductive glass

    DOEpatents

    Susman, S.; Volin, K.J.

    Described is an ionically conducting glass for use as a solid electrolyte in a power or secondary cell containing an alkali metal-containing anode and a cathode separated by an alkali metal ion conducting glass having an ionic transference number of unity and the general formula: A/sub 1 + x/D/sub 2-x/3/Si/sub x/P/sub 3 - x/O/sub 12 - 2x/3/, wherein A is a network modifier for the glass and is an alkali metal of the anode, D is an intermediate for the glass and is selected from the class consisting of Zr, Ti, Ge, Al, Sb, Be, and Zn and X is in the range of from 2.25 to 3.0. Of the alkali metals, Na and Li are preferred and of the intermediate, Zr, Ti and Ge are preferred.

  1. Highly Thermal Conductive Nanocomposites

    NASA Technical Reports Server (NTRS)

    Sun, Ya-Ping (Inventor); Connell, John W. (Inventor); Veca, Lucia Monica (Inventor)

    2015-01-01

    Disclosed are methods for forming carbon-based fillers as may be utilized in forming highly thermal conductive nanocomposite materials. Formation methods include treatment of an expanded graphite with an alcohol/water mixture followed by further exfoliation of the graphite to form extremely thin carbon nanosheets that are on the order of between about 2 and about 10 nanometers in thickness. Disclosed carbon nanosheets can be functionalized and/or can be incorporated in nanocomposites with extremely high thermal conductivities. Disclosed methods and materials can prove highly valuable in many technological applications including, for instance, in formation of heat management materials for protective clothing and as may be useful in space exploration or in others that require efficient yet light-weight and flexible thermal management solutions.

  2. Conductance of Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Datta, Supriyo; Anatram, M. P.

    1998-01-01

    The recent report of quantized conductance in a 4 m long multiwalled nanotube (MWNT) raises the exciting possibility of ballistic transport at room temperature over relatively long distances. We argue that this is made possible by the special symmetry of the eigenstates of the lowest propagating modes in metallic nanotubes which suppresses backscattering. This unusual effect is absent for the higher propagating modes so that transport is not ballistic once the bias exceeds the cut-off energy for the higher modes, which is estimated to be approximately 75 meV for nanotubes of diameter approximately 15 nm. Also, we show that the symmetry of the eigenstates can significantly affect their coupling to the reservoir and hence the contact resistance. A simple model is presented that can be used to understand the observed conductance-voltage characteristics.

  3. Electrically conductive alternating copolymers

    DOEpatents

    Aldissi, M.; Jorgensen, B.S.

    1987-08-31

    Polymers which are soluble in common organic solvents and are electrically conductive, but which also may be synthesized in such a manner that they become nonconductive. Negative ions from the electrolyte used in the electrochemical synthesis of a polymer are incorporated into the polymer during the synthesis and serve as a dopant. A further electrochemical step may be utilized to cause the polymer to be conductive. The monomer repeat unit is comprised of two rings, a pyrrole molecule joined to a thienyl group, or a furyl group, or a phenyl group. The individual groups of the polymers are arranged in an alternating manner. For example, the backbone arrangement of poly(furylpyrrole) is -furan-pyrrole-furan-pyrrole- furan-pyrrole. An alkyl group or phenyl group may be substituted for either or both of the hydrogen atoms of the pyrrole ring.

  4. Oxygen ion conducting materials

    DOEpatents

    Vaughey, John; Krumpelt, Michael; Wang, Xiaoping; Carter, J. David

    2005-07-12

    An oxygen ion conducting ceramic oxide that has applications in industry including fuel cells, oxygen pumps, oxygen sensors, and separation membranes. The material is based on the idea that substituting a dopant into the host perovskite lattice of (La,Sr)MnO.sub.3 that prefers a coordination number lower than 6 will induce oxygen ion vacancies to form in the lattice. Because the oxygen ion conductivity of (La,Sr)MnO.sub.3 is low over a very large temperature range, the material exhibits a high overpotential when used. The inclusion of oxygen vacancies into the lattice by doping the material has been found to maintain the desirable properties of (La,Sr)MnO.sub.3, while significantly decreasing the experimentally observed overpotential.

  5. Oxygen ion conducting materials

    DOEpatents

    Carter, J. David; Wang, Xiaoping; Vaughey, John; Krumpelt, Michael

    2004-11-23

    An oxygen ion conducting ceramic oxide that has applications in industry including fuel cells, oxygen pumps, oxygen sensors, and separation membranes. The material is based on the idea that substituting a dopant into the host perovskite lattice of (La,Sr)MnO.sub.3 that prefers a coordination number lower than 6 will induce oxygen ion vacancies to form in the lattice. Because the oxygen ion conductivity of (La,Sr)MnO.sub.3 is low over a very large temperature range, the material exhibits a high overpotential when used. The inclusion of oxygen vacancies into the lattice by doping the material has been found to maintain the desirable properties of (La,Sr)MnO.sub.3, while significantly decreasing the experimentally observed overpotential.

  6. Oxygen ion conducting materials

    DOEpatents

    Vaughey, John; Krumpelt, Michael; Wang, Xiaoping; Carter, J. David

    2003-01-01

    An oxygen ion conducting ceramic oxide that has applications in industry including fuel cells, oxygen pumps, oxygen sensors, and separation membranes. The material is based on the idea that substituting a dopant into the host perovskite lattice of (La,Sr)MnO.sub.3 that prefers a coordination number lower than 6 will induce oxygen ion vacancies to form in the lattice. Because the oxygen ion conductivity of (La,Sr)MnO.sub.3 is low over a very large temperature range, the material exhibits a high overpotential when used. The inclusion of oxygen vacancies into the lattice by doping the material has been found to maintain the desirable properties of (La,Sr)MnO.sub.3, while significantly decreasing the experimentally observed overpotential.

  7. Conduction cooled tube supports

    DOEpatents

    Worley, Arthur C.; Becht, IV, Charles

    1984-01-01

    In boilers, process tubes are suspended by means of support studs that are in thermal contact with and attached to the metal roof casing of the boiler and the upper bend portions of the process tubes. The support studs are sufficiently short that when the boiler is in use, the support studs are cooled by conduction of heat to the process tubes and the roof casing thereby maintaining the temperature of the stud so that it does not exceed 1400.degree. F.

  8. Thermally conductive polymers

    NASA Technical Reports Server (NTRS)

    Byrd, N. R.; Jenkins, R. K.; Lister, J. L. (Inventor)

    1971-01-01

    A thermally conductive polymer is provided having physical and chemical properties suited to use as a medium for potting electrical components. The polymer is prepared from hydroquinone, phenol, and formaldehyde, by conventional procedures employed for the preparation of phenol-formaldehyde resins. While the proportions of the monomers can be varied, a preferred polymer is formed from the monomers in a 1:1:2.4 molar or ratio of hydroquinone:phenol:formaldehyde.

  9. High conductivity composite metal

    DOEpatents

    Zhou, R.; Smith, J.L.; Embury, J.D.

    1998-01-06

    Electrical conductors and methods of producing them are disclosed, where the conductors possess both high strength and high conductivity. Conductors are comprised of carbon steel and a material chosen from a group consisting of copper, nickel, silver, and gold. Diffusion barriers are placed between these two materials. The components of a conductor are assembled and then the assembly is subjected to heat treating and mechanical deformation steps. 10 figs.

  10. High conductivity composite metal

    DOEpatents

    Zhou, Ruoyi; Smith, James L.; Embury, John David

    1998-01-01

    Electrical conductors and methods of producing them, where the conductors possess both high strength and high conductivity. Conductors are comprised of carbon steel and a material chosen from a group consisting of copper, nickel, silver, and gold. Diffusion barriers are placed between these two materials. The components of a conductor are assembled and then the assembly is subjected to heat treating and mechanical deformation steps.

  11. Canopy stomatal conductance

    SciTech Connect

    Baldocchi, D.D.; Luxmoore, R.J.; Hatfield, J.L.

    1989-07-14

    Stomata are major conduits for the diffusion of many trace gas species between leaves and the atmosphere. The role of the stomata on controlling gas exchange between the terrestrial biosphere and the atmosphere at the landscape, meso- and global-scales has only recently been recognized. Further advances in modelling large-scale trace gas exchange will depend on our ability to understand and model stomatal mechanics at the scale of the pertinent sub-unit, which is typically that of the canopy. This paper describes two approaches for estimating canopy stomatal conductance. One approach is based on 'bottom-up' scaling. This approach computes canopy stomatal conductance by integrating detailed leaf-level and environmentally-driven, physiological processes with the use of a detailed canopy micrometeorology model. The other approach is based on 'top-down' scaling. It interprets the integrated canopy stomatal conductance from measured fluxes of trace gas exchange. Frameworks for extending these scaling approaches to non-idea conditions are given. 96 refs., 5 figs.

  12. Conduction heat transfer solutions

    SciTech Connect

    VanSant, J.H.

    1983-08-01

    This text is a collection of solutions to a variety of heat conduction problems found in numerous publications, such as textbooks, handbooks, journals, reports, etc. Its purpose is to assemble these solutions into one source that can facilitate the search for a particular problem solution. Generally, it is intended to be a handbook on the subject of heat conduction. There are twelve sections of solutions which correspond with the class of problems found in each. Geometry, state, boundary conditions, and other categories are used to classify the problems. Each problem is concisely described by geometry and condition statements, and many times a descriptive sketch is also included. The introduction presents a synopsis on the theory, differential equations, and boundary conditions for conduction heat transfer. Some discussion is given on the use and interpretation of solutions. Supplementary data such as mathematical functions, convection correlations, and thermal properties are included for aiding the user in computing numerical values from the solutions. 155 figs., 92 refs., 9 tabs.

  13. Bradyarrhythmias and conduction blocks.

    PubMed

    Vogler, Julia; Breithardt, Günter; Eckardt, Lars

    2012-07-01

    Bradyarrhythmias are a common clinical finding and comprise a number of rhythm disorders including sinus node dysfunction and atrioventricular conduction disturbances. Clinical presentation varies from asymptomatic electrocardiogram findings (eg, during a routine examination) to a wide range of symptoms such as heart failure symptoms, near syncope or syncope, central nervous symptoms, or nonspecific and chronic symptoms such as dizziness or fatigue. Conditions resulting in bradyarrhythmic disorders are divided into intrinsic and extrinsic conditions causing damage to the conduction system. Furthermore bradyarrhythmias can be a normal physiologic reaction under certain circumstances. A proper diagnosis including a symptom-rhythm correlation is extremely important and is generally established by noninvasive diagnostic studies (12-lead electrocardiogram, Holter electrocardiogram, exercise testing, event recorder, implantable loop recorder). Invasive electrophysiologic testing is rarely required. If reversible extrinsic causes of bradyarrhythmias such as drugs (most often beta-blockers, glycosides and/or calcium channel blockers) or underlying treatable diseases are ruled out, cardiac pacing is usually the therapy of choice in symptomatic bradyarrhythmias. In this article of the current series on arrhythmias we will review the pathophysiology, diagnosis and treatment options of bradyarrhythmias, especially sinus node dysfunction and atrioventricular conduction blocks.

  14. Electrically Conductive Porous Membrane

    NASA Technical Reports Server (NTRS)

    Burke, Kenneth Alan (Inventor)

    2014-01-01

    The present invention relates to an electrically conductive membrane that can be configured to be used in fuel cell systems to act as a hydrophilic water separator internal to the fuel cell, or as a water separator used with water vapor fed electrolysis cells, or as a water separator used with water vapor fed electrolysis cells, or as a capillary structure in a thin head pipe evaporator, or as a hydrophobic gas diffusion layer covering the fuel cell electrode surface in a fuel cell.

  15. Conducting polymer ultracapacitor

    DOEpatents

    Shi, Steven Z.; Davey, John R.; Gottesfeld, Shimshon; Ren, Xiaoming

    2002-01-01

    A sealed ultracapacitor assembly is formed with first and second electrodes of first and second conducting polymers electrodeposited on porous carbon paper substrates, where the first and second electrodes each define first and second exterior surfaces and first and second opposing surfaces. First and second current collector plates are bonded to the first and second exterior surfaces, respectively. A porous membrane separates the first and second opposing surfaces, with a liquid electrolyte impregnating the insulating membrane. A gasket formed of a thermoplastic material surrounds the first and second electrodes and seals between the first and second current collector plates for containing the liquid electrolyte.

  16. Radiative thermal conduction fronts

    NASA Technical Reports Server (NTRS)

    Borkowski, Kazimierz J.; Balbus, Steven A.; Fristrom, Carl C.

    1990-01-01

    The discovery of the O VI interstellar absorption lines in our Galaxy by the Copernicus observatory was a turning point in our understanding of the Interstellar Medium (ISM). It implied the presence of widespread hot (approx. 10 to the 6th power K) gas in disk galaxies. The detection of highly ionized species in quasi-stellar objects' absorption spectra may be the first indirect observation of this hot phase in external disk galaxies. Previous efforts to understand extensive O VI absorption line data from our Galaxy were not very successful in locating the regions where this absorption originates. The location at interfaces between evaporating ISM clouds and hot gas was favored, but recent studies of steady-state conduction fronts in spherical clouds by Ballet, Arnaud, and Rothenflug (1986) and Bohringer and Hartquist (1987) rejected evaporative fronts as the absorption sites. Researchers report here on time-dependent nonequilibrium calculations of planar conductive fronts whose properties match well with observations, and suggest reasons for the difference between the researchers' results and the above. They included magnetic fields in additional models, not reported here, and the conclusions are not affected by their presence.

  17. Conduction heat transfer solutions

    SciTech Connect

    VanSant, J.H.

    1980-03-01

    This text is a collection of solutions to a variety of heat conduction problems found in numerous publications, such as textbooks, handbooks, journals, reports, etc. Its purpose is to assemble these solutions into one source that can facilitate the search for a particular problem solution. Generally, it is intended to be a handbook on the subject of heat conduction. This material is useful for engineers, scientists, technologists, and designers of all disciplines, particularly those who design thermal systems or estimate temperatures and heat transfer rates in structures. More than 500 problem solutions and relevant data are tabulated for easy retrieval. There are twelve sections of solutions which correspond with the class of problems found in each. Geometry, state, boundary conditions, and other categories are used to classify the problems. A case number is assigned to each problem for cross-referencing, and also for future reference. Each problem is concisely described by geometry and condition statements, and many times a descriptive sketch is also included. At least one source reference is given so that the user can review the methods used to derive the solutions. Problem solutions are given in the form of equations, graphs, and tables of data, all of which are also identified by problem case numbers and source references.

  18. [Female conduct disorders].

    PubMed

    Vloet, Timo D; Großheinrich, Nicola; Konrad, Kerstin; Freitag, Christine; Herpertz-Dahlmann, Beate

    2014-03-01

    The last few years have seen much research on girls with conduct disorder (CD). This article summarizes the gender-specific data regarding prevalence, differences with respect to symptomatology (e.g., subtypes of aggression, callous-unemotional (cu)-traits), and it presents data on the autonomic and neuroendocrine stress system as well as genetic, neurocognitive, and neuroimaging data. Differences in the impact of environmental factors on boys and girls for the development of CD are discussed. Taken together, the data indicate that there is great overlap in symptomatology, personality traits, and neurobiological aberrations in girls and boys with CD. Since fewer girls than boys exhibit CD symptomatology, further investigations on CD in girls might help to identify resilience factors that could improve future therapeutic interventions.

  19. Conductive elastomeric extensometer

    NASA Technical Reports Server (NTRS)

    Gause, R. L.; Glenn, C. G. (Inventor)

    1974-01-01

    An extensometer was used for measuring surface area changes of the human body caused by expansion and contraction of the body. A relatively thin and wide strain responsive conductive elastomeric band was adapted for application to a part of the body, such as around a limb or the trunk of the body. The elastomeric band is incorporated as a resistor in a balanced bridge circuit. Expansion or contraction of the portion of the body on which the elastomeric band is applied causes a change in the resistance of the band and a resultant imbalance of the bridge circuit. The output of the amplifier in volts is suitable for proving the desired reading through a recorder, oscilloscope or voltmeter.

  20. Ion-conducting membranes

    DOEpatents

    Masel, Richard L.; Chen, Qingmei; Liu, Zengcai; Kutz, Robert

    2016-06-21

    An ion conducting polymeric composition mixture comprises a copolymer of styrene and vinylbenzyl-R.sub.s. R.sub.s is selected from the group consisting of imidazoliums and pyridiniums. The composition contains 10%-90% by weight of vinylbenzyl-R.sub.s. The composition can further comprise a polyolefin comprising substituted polyolefins, a polymer comprising cyclic amine groups, a polymer comprising at least one of a phenylene group and a phenyl group, a polyamide, and/or the reaction product of a constituent having two carbon-carbon double bonds. The composition can be in the form of a membrane. In a preferred embodiment, the membrane is a Helper Membrane that increases the faradaic efficiency of an electrochemical cell into which the membrane is incorporated, and also allows product formation at lower voltages than in cells without the Helper Membrane.

  1. Lateral conduction infrared photodetector

    DOEpatents

    Kim, Jin K.; Carroll, Malcolm S.

    2011-09-20

    A photodetector for detecting infrared light in a wavelength range of 3-25 .mu.m is disclosed. The photodetector has a mesa structure formed from semiconductor layers which include a type-II superlattice formed of alternating layers of InAs and In.sub.xGa.sub.1-xSb with 0.ltoreq.x.ltoreq.0.5. Impurity doped regions are formed on sidewalls of the mesa structure to provide for a lateral conduction of photo-generated carriers which can provide an increased carrier mobility and a reduced surface recombination. An optional bias electrode can be used in the photodetector to control and vary a cut-off wavelength or a depletion width therein. The photodetector can be formed as a single-color or multi-color device, and can also be used to form a focal plane array which is compatible with conventional read-out integrated circuits.

  2. Carbon Fibers Conductivity Studies

    NASA Technical Reports Server (NTRS)

    Yang, C. Y.; Butkus, A. M.

    1980-01-01

    In an attempt to understand the process of electrical conduction in polyacrylonitrile (PAN)-based carbon fibers, calculations were carried out on cluster models of the fiber consisting of carbon, nitrogen, and hydrogen atoms using the modified intermediate neglect of differential overlap (MINDO) molecular orbital (MO) method. The models were developed based on the assumption that PAN carbon fibers obtained with heat treatment temperatures (HTT) below 1000 C retain nitrogen in a graphite-like lattice. For clusters modeling an edge nitrogen site, analysis of the occupied MO's indicated an electron distribution similar to that of graphite. A similar analysis for the somewhat less stable interior nitrogen site revealed a partially localized II electron distribution around the nitrogen atom. The differences in bonding trends and structural stability between edge and interior nitrogen clusters led to a two-step process proposed for nitrogen evolution with increasing HTT.

  3. Protein conducting nanopores

    NASA Astrophysics Data System (ADS)

    Harsman, Anke; Krüger, Vivien; Bartsch, Philipp; Honigmann, Alf; Schmidt, Oliver; Rao, Sanjana; Meisinger, Christof; Wagner, Richard

    2010-11-01

    About 50% of the cellular proteins have to be transported into or across cellular membranes. This transport is an essential step in the protein biosynthesis. In eukaryotic cells secretory proteins are transported into the endoplasmic reticulum before they are transported in vesicles to the plasma membrane. Almost all proteins of the endosymbiotic organelles chloroplasts and mitochondria are synthesized on cytosolic ribosomes and posttranslationally imported. Genetic, biochemical and biophysical approaches led to rather detailed knowledge on the composition of the translocon-complexes which catalyze the membrane transport of the preproteins. Comprehensive concepts on the targeting and membrane transport of polypeptides emerged, however little detail on the molecular nature and mechanisms of the protein translocation channels comprising nanopores has been achieved. In this paper we will highlight recent developments of the diverse protein translocation systems and focus particularly on the common biophysical properties and functions of the protein conducting nanopores. We also provide a first analysis of the interaction between the genuine protein conducting nanopore Tom40SC as well as a mutant Tom40SC (\\mathrm {S}_{54} \\to E ) containing an additional negative charge at the channel vestibule and one of its native substrates, CoxIV, a mitochondrial targeting peptide. The polypeptide induced a voltage-dependent increase in the frequency of channel closure of Tom40SC corresponding to a voltage-dependent association rate, which was even more pronounced for the Tom40SC S54E mutant. The corresponding dwelltime reflecting association/transport of the peptide could be determined with \\bar {t}_{\\mathrm {off}} \\cong 1.1 ms for the wildtype, whereas the mutant Tom40SC S54E displayed a biphasic dwelltime distribution (\\bar {t}_{\\mathrm {off}}^1 \\cong 0.4 ms \\bar {t}_{\\mathrm {off}}^2 \\cong 4.6 ms).

  4. Effect of Decitabine Combined with Unrelated Cord Blood Transplantation in an Adult Patient with -7/EVI1+ Acute Myeloid Leukemia: a Case Report and Literature Review.

    PubMed

    Jiang, Yi-Zhi; Su, Gui-Ping; Dai, Yan; He, He-Sheng; Huang, Lai-Quan; Sun, Zi-Min; Huang, Dong-Ping

    2015-01-01

    Patients with relapsed or refractory acute myeloid leukemia (rAML) have a poor prognosis if they do not undergo hematopoietic stem cell transplantation (HSCT). We describe a case herein of acute myeloid leukemia (AML) with monosomy 7 and EVI1(+)(-7/EVI1(+)) in a patient who failed to achieve a complete remission (CR) after two cycles of standard induction chemotherapy. He subsequently received decitabine (DAC) as "bridge therapy" and directly underwent unrelated cord blood transplantation (UCBT) due to the absence of an available sibling donor. Although DAC treatment did not induce CR, it did produce hematologic improvement and control disease progression with acceptable side effects, thus effectively bridging the time of donor search. Following UCBT, the marrow showed complete hematologic and cytogenetic remission. At present, 18 months after the transplantation, the patient's general condition is still good.

  5. Evolutionary plasticity in coccidia - striking morphological similarity of unrelated coccidia (apicomplexa) from related hosts: Eimeria spp. from African and Asian Pangolins (Mammalia: Pholidota).

    PubMed

    Jirků, Miloslav; Kvičerová, Jana; Modrý, David; Hypša, Václav

    2013-07-01

    Two morphologically similar, but phylogenetically unrelated Eimeria species from ancient mammals, African Tree Pangolin Phataginus tricuspis and Sunda Pangolin Manis javanica (Pholidota: Manidae), from two distant biogeographic realms (Afrotropical and Oriental), are characterized and compared morphologically and molecularly. Phylogenetic analyses produced an unstable topology. However, while precise position of the two Eimeria species from pangolins could not be firmly established due to the lack of related taxa, it is evident that they are not closely related and do not fall into any of the so far recognized eimerian lineages. Moreover, an eimerian found in P. tricuspis is described as a new species Eimeria nkaka n. sp., based on morphology of oocysts, endogenous developmental stages and sequence data. PMID:23837921

  6. A mutation in the neurofibromatosis type 2 tumor-suppressor gene, giving rise to widely different clinical phenotypes in two unrelated individuals

    SciTech Connect

    Bourn, D.; Carter, S.A.; Goodship, J.; Strachan, T. ); Evans, G.R.; Coakham, H.

    1994-07-01

    The authors have sought mutations in the recently identified neurofibromatosis type 2 (NF2) tumor-suppressor gene in a large panel of NF2 patients, using PCR-based SSCP and heteroduplex analysis, followed by cloning and sequencing of appropriate PCR products. Two unrelated NF2 patients were found to have identical nonsense mutations caused by a C-to-T transition in a CpG dinucleotide that is a potential mutational hot spot in the NF2 tumor-suppressor gene. Unexpectedly, the two individuals had widely different clinical phenotypes, representing the severe Wishart and mild Gardner clinical subtypes. Analysis of DNA samples from different tissues of the mildly affected patient suggests that he is a somatic mosaic for the mutation. 26 refs., 3 figs.

  7. New mutations in DYNC2H1 and WDR60 genes revealed by whole-exome sequencing in two unrelated Sardinian families with Jeune asphyxiating thoracic dystrophy.

    PubMed

    Cossu, Carla; Incani, Federica; Serra, Maria Luisa; Coiana, Alessandra; Crisponi, Giangiorgio; Boccone, Loredana; Rosatelli, Maria Cristina

    2016-04-01

    Jeune asphyxiating thoracic dystrophy (JATD; Jeune syndrome, MIM 208500) is a rare autosomal recessive chondrodysplasia, phenotypically overlapping with short-rib polydactyly syndromes (SRPS). JATD typical hallmarks include skeletal abnormalities such as narrow chest, shortened ribs, limbs shortened bones, extra fingers and toes (polydactyly), as well as extraskeletal manifestations (renal, liver and retinal disease). To date, disease-causing mutations have been found in several genes, highlighting a marked genetic heterogeneity that prevents a molecular diagnosis of the disease in most families. Here, we report the results of whole-exome sequencing (WES) carried out in four JATD cases, belonging to three unrelated families of Sardinian origin. The exome analysis allowed to identify mutations not previously reported in the DYNC2H1 (MIM 603297) and WDR60 (MIM 615462) genes, both codifying for ciliary intraflagellar transport components whose mutations are known to cause Jeune syndrome.

  8. Lexical embeddings produce interference when they are morphologically unrelated to the words in which they are contained: Evidence from eye movements

    PubMed Central

    Weingartner, Kristin M.; Juhasz, Barbara J.; Rayner, Keith

    2012-01-01

    Many words in the English language contain semantically and morphologically unrelated smaller words (e.g., room in groom). Recent findings indicate that a high frequency embedded word produces interference during visual word identification (e.g., Bowers, Davis, & Hanley, 2005; Davis, Perea, & Acha, 2009; Davis & Taft, 2005). In an eye movement experiment we examined whether lexical embeddings produce interference even when explicit judgments about lexicality or category membership are not solicited. Participants silently read sentences that each contained a target word with a lexical embedding. Fixation times were longer on target words that contained a higher frequency embedding compared to those that contained a lower frequency embedding. This finding indicates that a high frequency embedding interferes with word identification during silent reading and adds to a growing body of evidence that a word’s orthographic neighborhood includes embedded words. PMID:22900139

  9. New mutations in DYNC2H1 and WDR60 genes revealed by whole-exome sequencing in two unrelated Sardinian families with Jeune asphyxiating thoracic dystrophy.

    PubMed

    Cossu, Carla; Incani, Federica; Serra, Maria Luisa; Coiana, Alessandra; Crisponi, Giangiorgio; Boccone, Loredana; Rosatelli, Maria Cristina

    2016-04-01

    Jeune asphyxiating thoracic dystrophy (JATD; Jeune syndrome, MIM 208500) is a rare autosomal recessive chondrodysplasia, phenotypically overlapping with short-rib polydactyly syndromes (SRPS). JATD typical hallmarks include skeletal abnormalities such as narrow chest, shortened ribs, limbs shortened bones, extra fingers and toes (polydactyly), as well as extraskeletal manifestations (renal, liver and retinal disease). To date, disease-causing mutations have been found in several genes, highlighting a marked genetic heterogeneity that prevents a molecular diagnosis of the disease in most families. Here, we report the results of whole-exome sequencing (WES) carried out in four JATD cases, belonging to three unrelated families of Sardinian origin. The exome analysis allowed to identify mutations not previously reported in the DYNC2H1 (MIM 603297) and WDR60 (MIM 615462) genes, both codifying for ciliary intraflagellar transport components whose mutations are known to cause Jeune syndrome. PMID:26874042

  10. Evolutionary plasticity in coccidia - striking morphological similarity of unrelated coccidia (apicomplexa) from related hosts: Eimeria spp. from African and Asian Pangolins (Mammalia: Pholidota).

    PubMed

    Jirků, Miloslav; Kvičerová, Jana; Modrý, David; Hypša, Václav

    2013-07-01

    Two morphologically similar, but phylogenetically unrelated Eimeria species from ancient mammals, African Tree Pangolin Phataginus tricuspis and Sunda Pangolin Manis javanica (Pholidota: Manidae), from two distant biogeographic realms (Afrotropical and Oriental), are characterized and compared morphologically and molecularly. Phylogenetic analyses produced an unstable topology. However, while precise position of the two Eimeria species from pangolins could not be firmly established due to the lack of related taxa, it is evident that they are not closely related and do not fall into any of the so far recognized eimerian lineages. Moreover, an eimerian found in P. tricuspis is described as a new species Eimeria nkaka n. sp., based on morphology of oocysts, endogenous developmental stages and sequence data.

  11. The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia.

    PubMed

    La Nasa, Giorgio; Littera, Roberto; Locatelli, Franco; Lai, Sara; Alba, Francesco; Caocci, Giovanni; Lisini, Daniela; Nesci, Sonia; Vacca, Adriana; Piras, Eugenia; Bernardo, Maria Ester; Di Cesare-Merlone, Alessandra; Orrù, Sandro; Carcassi, Carlo

    2007-10-01

    The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30.2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (-14-bp/-14-bp vs +14-bp/+14-bp: Relative Risk = 15.0; 95% confidence interval 1.59-141.24; P = 0.008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation. PMID:17897304

  12. Metabolic risk in contemporary children is unrelated to socio-economic status: longitudinal study of a UK urban population (EarlyBird 42).

    PubMed

    Voss, Linda D; Hosking, Joanne; Metcalf, Brad S; Jeffery, Alison N; Frémeaux, Alissa E; Wilkin, Terence J

    2014-05-01

    Lifestyle interventions to improve health in young children tend to target areas of relative deprivation, but the evidence for so doing is largely historical. Accordingly, we have re-examined the link between deprivation, obesity and metabolic risk in contemporary UK children. Using a postcode-based index of multiple deprivation (IMD), we assessed 269 children from the community-based EarlyBird Study, attending 53 schools representing a wide socio-economic range. Annual measures of fatness from 5 to 8 yr included body mass index (BMI), waist circumference (WC), and sum of five skinfolds (SSF). A metabolic risk score, based on blood pressure, lipids and insulin resistance, was derived from annual fasting blood samples. There were no significant associations between deprivation and any measure of adiposity in girls (all p > 0.37). In boys, there was a weak but consistently inverse relationship between deprivation and WC (r = -0.19, p = 0.03) and BMI (r = -0.14, p = 0.09) at 8 yr. Changes in adiposity over 3 yr were unrelated to deprivation in boys. In girls there was a slight but significant increase in SSF only (1 mm/yr per 20 IMD units, p = 0.001). Importantly, in both genders, metabolic risk score was unrelated to deprivation throughout (r values -0.05 to -0.13, all p > 0.12), as was change in metabolic risk (all p > 0.30). Our data do not support the assumption that obesity, metabolic disturbance and thus risk of type 2 diabetes are more prevalent among poorer children. In today's increasingly obesogenic environment, youngsters from all backgrounds appear to be vulnerable, with population-wide implications for public health spending, and the prevention of diabetes in contemporary youth. PMID:24827703

  13. Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study

    PubMed Central

    Youngster, Ilan; Sauk, Jenny; Pindar, Christina; Wilson, Robin G.; Kaplan, Jess L.; Smith, Mark B.; Alm, Eric J.; Gevers, Dirk; Russell, George H.; Hohmann, Elizabeth L.

    2014-01-01

    Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2–16) relapses prior to study enrollment, with 5 (range, 3–15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5–10) the day prior to FMT to 2 (IQR, 1–2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2–6) before transplant to 8 (IQR, 5–9) after transplant. No serious or unexpected adverse events occurred. Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. Clinical Trials Registration. NCT01704937. PMID:24762631

  14. Metabolic risk in contemporary children is unrelated to socio-economic status: longitudinal study of a UK urban population (EarlyBird 42).

    PubMed

    Voss, Linda D; Hosking, Joanne; Metcalf, Brad S; Jeffery, Alison N; Frémeaux, Alissa E; Wilkin, Terence J

    2014-05-01

    Lifestyle interventions to improve health in young children tend to target areas of relative deprivation, but the evidence for so doing is largely historical. Accordingly, we have re-examined the link between deprivation, obesity and metabolic risk in contemporary UK children. Using a postcode-based index of multiple deprivation (IMD), we assessed 269 children from the community-based EarlyBird Study, attending 53 schools representing a wide socio-economic range. Annual measures of fatness from 5 to 8 yr included body mass index (BMI), waist circumference (WC), and sum of five skinfolds (SSF). A metabolic risk score, based on blood pressure, lipids and insulin resistance, was derived from annual fasting blood samples. There were no significant associations between deprivation and any measure of adiposity in girls (all p > 0.37). In boys, there was a weak but consistently inverse relationship between deprivation and WC (r = -0.19, p = 0.03) and BMI (r = -0.14, p = 0.09) at 8 yr. Changes in adiposity over 3 yr were unrelated to deprivation in boys. In girls there was a slight but significant increase in SSF only (1 mm/yr per 20 IMD units, p = 0.001). Importantly, in both genders, metabolic risk score was unrelated to deprivation throughout (r values -0.05 to -0.13, all p > 0.12), as was change in metabolic risk (all p > 0.30). Our data do not support the assumption that obesity, metabolic disturbance and thus risk of type 2 diabetes are more prevalent among poorer children. In today's increasingly obesogenic environment, youngsters from all backgrounds appear to be vulnerable, with population-wide implications for public health spending, and the prevention of diabetes in contemporary youth.

  15. Probability of Finding Marrow Unrelated Donor (MUD) for an Indian patient in a Multi-national Human Leukocyte Antigen (HLA) Registry.

    PubMed

    Tiwari, Aseem K; Bhati-Kushwaha, Himakshi; Kukreja, Pooja; Mishra, Vikash C; Tyagi, Neetu; Sharma, Ashish; Raina, Vimarsh

    2015-06-01

    With an increase in the number of transplants happening globally, hematopoietic stem cells (HSC) transplantation from matched unrelated donor (MUD) has begun. The increasing trend of MUD transplants across countries has been largely facilitated with the conspicuous growth of volunteer HSC donor noted in the last decade i.e. 8 million HSC donors in 2002 to more than 22 million in 2013 registered in 71 member registries of the Bone Marrow Donor Worldwide (BMDW). Some populations of the world are still very poorly represented in these registries. Since, the chances of successful engraftment and disease free survival are directly proportional to the HLA compatibility between the recipient and the prospective donor, the diversity of the HLA system at the antigenic and allelic level and the heterogeneity of HLA data of the registered donors has a bearing on the probability of finding a volunteer unrelated HSC donor for patients from such populations. In the present study 126 patients were identified suffering from hematological diseases requiring MUD transplant. Their HLA typing was performed and search was done using BMDW database. The search results for these Indian patients in the multinational registry as well as in the Indian Registries were analyzed using mean, range, standard deviation and finally evaluated in terms of probability for finding matched donor (MUD). Total Asian population is only 11 % in the BMDW making it difficult to find a MUD for an Asian patient. The current study supports this, experimentally; revealing that the probability of finding an allele match for an Indian patient in the multinational Human Leukocyte Antigen (HLA) registries is 16 % and a dismal 0.008 % in the Indian registries (donors in Indian registries is just 33,678 as compared to 22.5 million in BMDW). This greatly, emphasizes on enhancing the number of Indian donors in Indian and multi-national registries. PMID:25825557

  16. Comparison of allogeneic stem cell transplantation from familial-mismatched/haploidentical donors and from unrelated donors in adults with high-risk acute myelogenous leukemia.

    PubMed

    Cho, Byung-Sik; Yoon, Jae-Ho; Shin, Seung-Hwan; Yahng, Seung-Ah; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won; Kim, Hee-Je

    2012-10-01

    To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed.

  17. A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome

    PubMed Central

    Al-Haggar, Mohammad; Madej-Pilarczyk, Agnieszka; Kozlowski, Lukasz; Bujnicki, Janusz M; Yahia, Sohier; Abdel-Hadi, Dina; Shams, Amany; Ahmad, Nermin; Hamed, Sahar; Puzianowska-Kuznicka, Monika

    2012-01-01

    Mandibuloacral dysplasia (MAD) is a rare disease resulting from a mutation of LMNA gene encoding lamins A and C. The most common mutation associated with this disease is a homozygous arginine 527 replacement by histidine. Three female patients originating from two unrelated families from Northeast Egypt were examined. Their growth was retarded; they had microcephaly, widened cranial sutures, prominent eyes and cheeks, micrognathia, dental crowding, hypoplastic mandible, acro-osteolysis of distal phalanges, and joint contractures. In addition, they presented some progeroid features, such as pinched nose, premature loss of teeth, loss of hair, scleroderma-like skin atrophy, spine rigidity, and waddling gait. The clinical presentation of the disease varied between the patient originating from Family 1 and patients from Family 2, suggesting that unknown, possibly epigenetic factors, modify the course of the disease. The first symptoms of the disease appeared at the age of 2.5 (a girl from Family 1), 5, and 3 years (girls from Family 2). All patients had the same, novel homozygous c.1580G>T LMNA mutation, resulting in the replacement of arginine 527 by leucine. Computational predictions of such substitution effects suggested that it might alter protein stability and increase the tendency for protein aggregation, and as a result, might influence its interaction with other proteins. In addition, restriction fragment-length polymorphism analysis performed in 178 unrelated individuals showed that up to 1.12% of inhabitants of Northeast Egypt might be heterozygous carriers of this mutation, suggesting the presence of a founder effect in this area. PMID:22549407

  18. Unrelated donor hematopoietic stem cell transplantation for the treatment of non-malignant genetic diseases: An alemtuzumab based regimen is associated with cure of clinical disease; earlier clearance of alemtuzumab may be associated with graft rejection.

    PubMed

    Abdel-Azim, Hisham; Mahadeo, Kris Michael; Zhao, Quan; Khazal, Sajad; Kohn, Donald B; Crooks, Gay M; Shah, Ami J; Kapoor, Neena

    2015-11-01

    Hematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUD), offers potentially curative therapy for patients with non-malignant genetic diseases. In this pilot study conducted from 2006 to 2014, we report the outcomes of 15 patients with non-malignant genetic diseases who received a myeloablative regimen with a reduced cyclophosphamide dose, adjunctive serotherapy and MUD HSCT [intravenous alemtuzumab (52 mg/m(2) ), busulfan (16 mg/kg), fludarabine (140mg/m(2) ), and cyclophosphamide (105 mg/kg)]. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus/cyclosporine and methylprednisolone. Median (range) time to neutrophil engraftment (>500 cells/µL) and platelet engraftment (>20,000/mm(3) ) were 15 (12-28) and 25 (17-30) days, respectively. At a median follow-up of 2 (0.2-5.4) years, the overall survival (OS) was 93.3% (95% CI: 0.61-0.99) and disease-free survival (DFS) was 73.3% (95% CI: 0.44-0.89). Among this small sample, earlier alemtuzumab clearance was significantly associated with graft rejection (P = 0.047), earlier PHA response (P = 0.009) and a trend toward earlier recovery of recent thymic emigrants (RTE) (P = 0.06). This regimen was associated with durable donor engraftment and relatively low rates of regimen related toxicity (RRT); future alemtuzumab pharmacokinetic studies may improve outcomes, by allowing targeted alemtuzumab clearance to reduce graft rejection and promote more rapid immune reconstitution.

  19. Thermal Contact Conductance

    NASA Technical Reports Server (NTRS)

    Salerno, Louis J.; Kittel, Peter

    1997-01-01

    The performance of cryogenic instruments is often a function of their operating temperature. Thus, designers of cryogenic instruments often are required to predict the operating temperature of each instrument they design. This requires accurate thermal models of cryogenic components which include the properties of the materials and assembly techniques used. When components are bolted or otherwise pressed together, a knowledge of the thermal performance of such joints are also needed. In some cases, the temperature drop across these joints represents a significant fraction of the total temperature difference between the instrument and its cooler. While extensive databases exist on the thermal properties of bulk materials, similar databases for pressed contacts do not. This has often lead to instrument designs that avoid pressed contacts or to the over-design of such joints at unnecessary expense. Although many people have made measurements of contact conductances at cryogenic temperatures, this data is often very narrow in scope and even more often it has not been published in an easily retrievable fashion, if published at all. This paper presents a summary of the limited pressed contact data available in the literature.

  20. Increased Locomotor Activity and Non-Selective Attention and Impaired Learning Ability in SD Rats after Lentiviral Vector-Mediated RNA Interference of Homer 1a in the Brain

    PubMed Central

    Hong, Qin; Yang, Lei; Zhang, Min; Pan, Xiao-Qin; Guo, Mei; Fei, Li; Tong, Mei-Ling; Chen, Rong-Hua; Guo, Xi-Rong; Chi, Xia

    2013-01-01

    Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD. PMID:23289010

  1. Electrically Conductive Paints for Satellites

    NASA Technical Reports Server (NTRS)

    Gilligan, J. E.; Wolf, R. E.; Ray, C.

    1977-01-01

    A program was conducted to develop and test electrically conductive paint coatings for spacecraft. A wide variety of organic and inorganic coatings were formulated using conductive binders, conductive pigments, and similar approaches. Z-93, IITRI's standard specification inorganic thermal control coating, exhibits good electrical properties and is a very space-stable coating system. Several coatings based on a conductive pigment (antimony-doped tin oxide) in silicone and silicate binders offer considerable promise. Paint systems using commercially available conductive polymers also appear to be of interest, but will require substantial development. Evaluations were made based on electrical conductivity, paint physical properties, and the stability of spectral reflectance in space environment testing.

  2. Conductive lithium storage electrode

    DOEpatents

    Chiang, Yet-Ming; Chung, Sung-Yoon; Bloking, Jason T.; Andersson, Anna M.

    2012-04-03

    A compound comprising a composition A.sub.x(M'.sub.1-aM''.sub.a).sub.y(XD.sub.4).sub.z, A.sub.x(M'.sub.1-aM''.sub.a).sub.y(DXD.sub.4).sub.z, or A.sub.x(M'.sub.1-aM''.sub.a).sub.y(X.sub.2D.sub.7).sub.z, and have values such that x, plus y(1-a) times a formal valence or valences of M', plus ya times a formal valence or valence of M'', is equal to z times a formal valence of the XD.sub.4, X.sub.2D.sub.7, or DXD.sub.4 group; or a compound comprising a composition (A.sub.1-aM''.sub.a).sub.xM'.sub.y(XD.sub.4).sub.z, (A.sub.1-aM''.sub.a).sub.xM'.sub.y(DXD.sub.4).sub.z (A.sub.1-aM''.sub.a).sub.xM'.sub.y(X.sub.2D.sub.7).sub.z and have values such that (1-a).sub.x plus the quantity ax times the formal valence or valences of M'' plus y times the formal valence or valences of M' is equal to z times the formal valence of the XD.sub.4, X.sub.2D.sub.7 or DXD.sub.4 group. In the compound, A is at least one of an alkali metal and hydrogen, M' is a first-row transition metal, X is at least one of phosphorus, sulfur, arsenic, molybdenum, and tungsten, M'' any of a Group IIA, IIIA, IVA, VA, VIA, VIIA, VIIIA, IB, IIB, IIIB, IVB, VB, and VIB metal, D is at least one of oxygen, nitrogen, carbon, or a halogen, 0.0001conductivity at 27.degree. C. of at least about 10.sup.-8 S/cm. The compound can be a doped lithium phosphate that can intercalate lithium or hydrogen. The compound can be used in an electrochemical device including electrodes and storage batteries and can have a gravimetric capacity of at least about 80 mAh/g while being charged/discharged at greater than about C rate of the compound.

  3. Conductive lithium storage electrode

    DOEpatents

    Chiang, Yet-Ming; Chung, Sung-Yoon; Bloking, Jason T.; Andersson, Anna M.

    2008-03-18

    A compound comprising a composition A.sub.x(M'.sub.1-aM''.sub.a).sub.y(XD.sub.4).sub.z, A.sub.x(M'.sub.1-aM''.sub.a).sub.y(DXD.sub.4).sub.z, or A.sub.x(M'.sub.1-aM''.sub.a).sub.y(X.sub.2D.sub.7).sub.z, and have values such that x, plus y(1-a) times a formal valence or valences of M', plus ya times a formal valence or valence of M'', is equal to z times a formal valence of the XD.sub.4, X.sub.2D.sub.7, or DXD.sub.4 group; or a compound comprising a composition (A.sub.1-aM''.sub.a).sub.xM'.sub.y(XD.sub.4).sub.z, (A.sub.1-aM''.sub.a).sub.xM'.sub.y(DXD.sub.4).sub.z(A.sub.1-aM''.sub.a).s- ub.xM'.sub.y(X.sub.2D.sub.7).sub.z and have values such that (1-a).sub.x plus the quantity ax times the formal valence or valences of M'' plus y times the formal valence or valences of M' is equal to z times the formal valence of the XD.sub.4, X.sub.2D.sub.7 or DXD.sub.4 group. In the compound, A is at least one of an alkali metal and hydrogen, M' is a first-row transition metal, X is at least one of phosphorus, sulfur, arsenic, molybdenum, and tungsten, M'' any of a Group IIA, IIIA, IVA, VA, VIA, VIIA, VIIIA, IB, IIB, IIIB, IVB, VB, and VIB metal, D is at least one of oxygen, nitrogen, carbon, or a halogen, 0.0001conductivity at 27.degree. C. of at least about 10.sup.-8 S/cm. The compound can be a doped lithium phosphate that can intercalate lithium or hydrogen. The compound can be used in an electrochemical device including electrodes and storage batteries and can have a gravimetric capacity of at least about 80 mAh/g while being charged/discharged at greater than about C rate of the compound.

  4. Comparing proton conductivity of polymer electrolytes by percent conducting volume

    SciTech Connect

    Kim, Yu Seung; Pivovar, Bryan

    2009-01-01

    Proton conductivity of sulfonated polymers plays a key role in polymer electrolyte membrane fuel cells. Mass based water uptake and ion exchange capacity of sulfonated polymers have been failed to correlating their proton conductivity. In this paper, we report a length scale parameter, percent conductivity volume, which is rather simply obtained from the chemical structure of polymer to compare proton conductivity of wholly aromatic sulfonated polymer perflurosulfonic acid. Morphology effect on proton conductivity at lower RH conditions is discussed using the percent conductivity volume parameter.

  5. Reduced Intensity Allogeneic Transplant In Patients Older Than 55 Years: Unrelated Umbilical Cord Blood Is Safe And Effective For Patients Without A Matched Related Donor

    PubMed Central

    Majhail, Navneet S; Brunstein, Claudio G; Tomblyn, Marcie; Thomas, Avis J; Miller, Jeffrey S; Arora, Mukta; Kaufman, Dan S; Burns, Linda J; Slungaard, Arne; McGlave, Philip B; Wagner, John E; Weisdorf, Daniel J

    2009-01-01

    The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source to suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients and compared the transplant related mortality (TRM) and overall survival of RIC HCT in patients older than 55 years using either MRD (n=47) or, in patients with no 5/6 or 6/6 HLA compatible related donors, UCB (n=43). RIC regimen consisted of total-body irradiation (200 cGy) and either cyclophosphamide and fludarabine (n=69), or busulfan and fludarabine (n=16) or busulfan and cladribine (n=5). The median age of MRD and UCB cohorts was 58 (range, 55-70) and 59 (range, 55-69) years, respectively. AML/MDS (50%) was the most common diagnosis. All MRD grafts were 6 of 6 HLA matched to the recipient. Among patients undergoing UCB HCT, 88% received two UCB units to optimize cell dose and 93% received 1-2 HLA mismatched grafts. The median followup for survivors was 27 (range, 12-61) months. The 3-year probabilities of progression-free survival (30% vs. 34%, p=0.98) and overall survival (43% vs. 34%, p=0.57) were similar for recipients of MRD and UCB. The cumulative incidence of grade 2-4 acute graft-versus-host disease (42% vs. 49%, p=0.20) and TRM at 180-days (23% vs. 28%, p=0.36) were comparable. However, UCB recipients had a lower incidence of chronic graft-versus-host disease at 1-year (40% vs. 17%, p=0.02). On multivariate analysis, graft type had no impact on TRM or survival and HCT comorbidity index score was the only factor independently predictive for these endpoints. Our study supports the use of HLA mismatched UCB as an alternative graft source for older patients who need a transplant but do not have a MRD. The use of RIC and UCB extends the

  6. Electrical Conductivity of Ferritin Proteins by Conductive AFM

    NASA Technical Reports Server (NTRS)

    Xu, Degao; Watt, Gerald D.; Harb, John N.; Davis, Robert C.

    2005-01-01

    Electrical conductivity measurements were performed on single apoferritin and holoferritin molecules by conductive atomic force microscopy. Conductivity of self-assembled monolayer films of ferritin molecules on gold surfaces was also measured. Holoferritin was 5-25 times more conductive than apoferritin, indicating that for holoferritin most electron-transfer goes through the ferrihydrite core. With 1 V applied, the average electrical currents through single holoferritin and apoferritin molecules were 2.6 PA and 0.19 PA, respectively.

  7. Unrelated Donor Stem Cell Transplantation

    ClinicalTrials.gov

    2013-12-05

    Severe Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Myeloproliferative Syndromes; Chronic Myelogenous Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Multiple Myeloma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Large Granulocytic Leukemia

  8. Non-Selective Cannabinoid Receptor Antagonists, Hinokiresinols Reduce Infiltration of Microglia/Macrophages into Ischemic Brain Lesions in Rat via Modulating 2-Arachidonolyglycerol-Induced Migration and Mitochondrial Activity

    PubMed Central

    Anthony Jalin, Angela M. A.; Rajasekaran, Maheswari; Prather, Paul L.; Kwon, Jin Sun; Gajulapati, Veeraswamy; Choi, Yongseok; Kim, Chunsook; Pahk, Kisoo; Ju, Chung; Kim, Won-Ki

    2015-01-01

    Growing evidence suggests that therapeutic strategies to modulate the post-ischemic inflammatory responses are promising approaches to improve stroke outcome. Although the endocannabinoid system has been emerged as an endogenous therapeutic target to regulate inflammation after stroke insult, the downstream mechanisms and their potentials for therapeutic intervention remain controversial. Here we identified trans- and cis-hinokiresinols as novel non-selective antagonists for two G-protein-coupled cannabinoid receptors, cannabinoid receptor type 1 and type 2. The Electric Cell-substrate Impedance Sensing and Boyden chamber migration assays using primary microglial cultures revealed that both hinokiresinols significantly inhibited an endocannabinoid, 2-arachidonoylglycerol-induced migration. Hinokiresinols modulated 2-arachidonoylglycerol-induced mitochondrial bioenergetics in microglia as evidenced by inhibition of ATP turnover and reduction in respiratory capacity, thereby resulting in impaired migration activity. In rats subjected to transient middle cerebral artery occlusion (1.5-h) followed by 24-h reperfusion, post-ischemic treatment with hinokiresinols (2 and 7-h after the onset of ischemia, 10 mg/kg) significantly reduced cerebral infarct and infiltration of ED1-positive microglial/macrophage cells into cerebral ischemic lesions in vivo. Co-administration of exogenous 2-AG (1 mg/kg, i.v., single dose at 2 h after starting MCAO) abolished the protective effect of trans-hinokiresionol. These results suggest that hinokiresinols may serve as stroke treatment by targeting the endocannabinoid system. Alteration of mitochondrial bioenergetics and consequent inhibition of inflammatory cells migration may be a novel mechanism underlying anti-ischemic effects conferred by cannabinoid receptor antagonists. PMID:26517721

  9. Undergraduate Conductors' and Conducting Teachers' Perceptions of Basic Conducting Efficacy

    ERIC Educational Resources Information Center

    Silvey, Brian A.; Baumgartner, Christopher M.

    2016-01-01

    The purpose of this study was to examine undergraduate conductors' and conducting teachers' perceptions about basic conducting efficacy. At the beginning and end of the semester, undergraduate students (N = 19) enrolled in a basic conducting course (a) were surveyed about the importance of certain skills necessary for being an effective conductor…

  10. The electrical conductivity and surface conduction of consolidated rock cores.

    PubMed

    Alkafeef, Saad F; Alajmi, Abdullah F

    2007-05-15

    A fully computerized high-pressure and high-temperature core holder device is simultaneously used to determine the electrical conductivity, zeta potential, and surface conductivity of consolidated rock cores in aqueous and nonaqueous systems. The total electrical conductivity of rock cores was determined by coupling streaming current and potential measurements. This shows that neglecting the surface conductivity Ksigma is crucial to converting the streaming potential into zeta potentials. It is observed that plots of the core total conductivity as a function of the electrolyte conductivity KL exhibit two behaviors. At low ionic strength, the core conductivity clearly depends on the contribution of surface conductivity behind the slip plane, whereas at higher ionic strength, the magnitude of the surface conductivity becomes negligible. The electrical conductivity of rock cores was found to be in good agreement with the O'Brien theory and the Briggs method. The contribution of the stagnant layer to the surface conductivity in nonaqueous systems has been shown to be significant. This shows that the stagnant layer displays significantly different behavior in different nonaqueous systems, depending on the core porosity and the double-layer overlap. The results indicate that the application of electrokinetics in petroleum reservoirs can provide important insights into reservoir fluid flow characterization.

  11. Thermal Conductivity of Coated Paper

    SciTech Connect

    Kerr, Lei L; Pan, Yun-Long; Dinwiddie, Ralph Barton; Wang, Hsin; Peterson, Robert C.

    2009-01-01

    In this paper, we introduce a method for measuring the thermal conductivity of paper using a hot disk system. To the best of our knowledge, few publications are found discussing the thermal conductivity of a coated paper although it is important to various forms of today s digital printing where heat is used for imaging as well as for toner fusing. This motivates us to investigate the thermal conductivity of paper coating. Our investigation demonstrates that thermal conductivity is affected by the coat weight and the changes in the thermal conductivity affect ink gloss and density. As the coat weight increases, the thermal conductivity increases. Both the ink gloss and density decrease as the thermal conductivity increases. The ink gloss appears to be more sensitive to the changes in the thermal conductivity.

  12. Hydrodynamic focusing of conducting fluids for conductivity-based biosensors.

    PubMed

    Nasir, Mansoor; Ateya, Daniel A; Burk, Diana; Golden, Joel P; Ligler, Frances S

    2010-02-15

    Hydrodynamic focusing of a conducting fluid by a non-conducting fluid to form a constricted current path between two sensing electrodes is implemented in order to enhance the sensitivity of a 4-electrode conductance-based biosensor. The sensor has a simple two-inlet T-junction design and performs four-point conductivity measurements to detect particles immobilized between the sensing electrode pair. Computational simulations conducted in conjunction with experimental flow studies using confocal microscopy show that a flat profile for the focused layer is dependent on the Reynolds number for the chosen flow parameters. The results also indicate that a flat focused layer is desirable for both increased sensitivity as well as surface-binding efficiency. Proof of concept for conductance measurements in a hydrodynamically focused conducting fluid was demonstrated with entrapped magnetic beads. PMID:19932019

  13. Mineralization- and remodeling-unrelated improvement of the post-yield properties of rat cortical bone by high doses of olpadronate.

    PubMed

    Capozza, R F; Mondelo, N; Reina, P S; Nocciolino, L; Meta, M; Roldan, E J; Ferretti, J L; Cointry, G R

    2013-06-01

    Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons. This study analyzes some effects of olpadronate on cortical bone modeling and post-yield properties in femurs diaphyses (virtually only-modeling bones) of young rats by mid-diaphyseal pQCT scans and bending tests. We studied 20/22 male/female animals traetad orally with olpadronate (45-90 mg/kg/d, 3 months) and 8/9 untreated controls. Both OPD doses enhanced diaphyseal cross-sectional moments of inertia (CSMI) with no change in cortical vBMD and elastic modulus. Yield stiffness and strength were mildly increased. Post-yield strength, deflection and energy absorption were strikingly enhanced. Ultimate strength was enhanced mainly because of effects on bone mass/geometry and post-yield properties. The large improvement of post-yield properties could be explained by improvements in bone geometry. Improvements in bone mass/geometry over weight-bearing needs suggest an enhanced modeling-related response to mechanical stimuli. Effects on tissue microstructural factors (not measured) could not be excluded. Results reveal novel olpadronate effects on bone strength and toughness unrelated to tissue mineralization and stiffness, even at high doses. Further studies could establish whether this could also occur in modeling-remodeling skeletons. If so, they could counteract the negative impact of anti-remodeling effects of bisphosphonates on bone strength.

  14. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse.

    PubMed

    Imahashi, Nobuhiko; Ohashi, Haruhiko; Terakura, Seitaro; Miyao, Kotaro; Sakemura, Reona; Kato, Tomonori; Sawa, Masashi; Yokohata, Emi; Kurahashi, Shingo; Ozawa, Yukiyasu; Nishida, Tetsuya; Kiyoi, Hitoshi; Watamoto, Koichi; Kohno, Akio; Kasai, Masanobu; Kato, Chiaki; Iida, Hiroatsu; Naoe, Tomoki; Miyamura, Koichi; Murata, Makoto

    2015-07-01

    Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen. PMID:25680895

  15. Population cycles are highly correlated over long time series and large spatial scales in two unrelated species: Greater sage-grouse and cottontail rabbits

    USGS Publications Warehouse

    Fedy, B.C.; Doherty, K.E.

    2011-01-01

    Animal species across multiple taxa demonstrate multi-annual population cycles, which have long been of interest to ecologists. Correlated population cycles between species that do not share a predator-prey relationship are particularly intriguing and challenging to explain. We investigated annual population trends of greater sage-grouse (Centrocercus urophasianus) and cottontail rabbits (Sylvilagus sp.) across Wyoming to explore the possibility of correlations between unrelated species, over multiple cycles, very large spatial areas, and relatively southern latitudes in terms of cycling species. We analyzed sage-grouse lek counts and annual hunter harvest indices from 1982 to 2007. We show that greater sage-grouse, currently listed as warranted but precluded under the US Endangered Species Act, and cottontails have highly correlated cycles (r = 0. 77). We explore possible mechanistic hypotheses to explain the synchronous population cycles. Our research highlights the importance of control populations in both adaptive management and impact studies. Furthermore, we demonstrate the functional value of these indices (lek counts and hunter harvest) for tracking broad-scale fluctuations in the species. This level of highly correlated long-term cycling has not previously been documented between two non-related species, over a long time-series, very large spatial scale, and within more southern latitudes. ?? 2010 US Government.

  16. Establishment of Definitions and Review Process for Consistent Adjudication of Cause-Specific Mortality After Allogeneic Unrelated Donor Hematopoietic Cell Transplantation

    PubMed Central

    Preus, Leah; Zhu, Xiaochun; Hansen, John A.; Martin, Paul J.; Yan, Li; Liu, Song; Spellman, Stephen; Tritchler, David; Clay, Alyssa

    2015-01-01

    Clinical trials commonly use adjudication committees to refine endpoints, but observational research or genome-wide association studies rarely do. Our goals were to establish definitions of cause-specific death after unrelated donor allogeneic hematopoietic cell transplantation (URD-HCT), estimate discordance between reported and adjudicated cause-specific death, and identify factors contributing to inconsistency in cause-specific deathdetermination. A consensus panel adjudicated cause-specific deathin 1,484 patients who died within 1 year after HCT, derived from 3,532 acute leukemia or myelodysplasia patients after URD-HCT 2000-2011 reported by 151 U.S. transplant centers to CIBMTR. Deaths were classified as disease-related (DRM) or transplant-related (TRM). The panel agreed with >99% of deaths reported by centers as DRM and 80% reported as TRM. Year of transplant (cohort effect) and disease status significantly influenced agreement between panel and centers. Sensitivity analysis of deaths <100 days post-transplant yielded lowest agreement between the panel and centers for myelodysplastic syndrome patients. Standard pre-defined criteria for adjudicating cause-specific deathled to consistent application to similar clinical scenarios and clearer delineation of cause-specific deathcategories. Other studies of competing events like cancer-specific vs treatment-related mortality would benefit from our results. Our detailed algorithm should result in more consistent reporting of cause-specific deathby centers. PMID:26028504

  17. Eggshell porosity covaries with egg size among female House Wrens (Troglodytes aedon) but is unrelated to incubation onset and egg-laying order within clutches

    PubMed Central

    Bowers, E.K.; White, A.; Lang, A.; Podgorski, L.; Thompson, C.F.; Sakaluk, S.K.; Jaeckle, W.B.; Harper, R.G.

    2015-01-01

    In birds, the duration of egg incubation (the time from incubation onset to hatching) can affect multiple components of nest success, but what affects incubation duration? Previous studies suggest that incubation duration is affected by both parental behavior and components of the egg, which have yet to be determined. One egg component that may be related to incubation behavior and the time until hatching is eggshell porosity, which affects the exchange of metabolic gasses and water vapor across the shell and, thus, the speed of embryonic development and incubation duration. We tested whether eggshell porosity was associated with the timing of incubation onset by female House Wrens (Troglodytes aedon Vieillot, 1809), and whether porosity varied within clutches in a manner that might be associated with incubation periods and hatching patterns (i.e., synchronous vs. asynchronous hatching). Eggshell porosity was unrelated to the onset of maternal incubation and did not differ between early and later-laid eggs within clutches, but differed significantly among females and covaried with egg size. We conclude that producing all eggshells of similar porosity within clutches, while adjusting incubation onset once most or all eggs are laid, provide facultative maternal control over variation in hatching patterns. PMID:26146408

  18. Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and functional variants in association with leprosy in unrelated indian population groups.

    PubMed

    Chopra, Rupali; Ali, Shafat; Srivastava, Amit K; Aggarwal, Shweta; Kumar, Bhupender; Manvati, Siddharth; Kalaiarasan, Ponnusamy; Jena, Mamta; Garg, Vijay K; Bhattacharya, Sambit N; Bamezai, Rameshwar N K

    2013-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.

  19. Population cycles are highly correlated over long time series and large spatial scales in two unrelated species: greater sage-grouse and cottontail rabbits.

    PubMed

    Fedy, Bradley C; Doherty, Kevin E

    2011-04-01

    Animal species across multiple taxa demonstrate multi-annual population cycles, which have long been of interest to ecologists. Correlated population cycles between species that do not share a predator-prey relationship are particularly intriguing and challenging to explain. We investigated annual population trends of greater sage-grouse (Centrocercus urophasianus) and cottontail rabbits (Sylvilagus sp.) across Wyoming to explore the possibility of correlations between unrelated species, over multiple cycles, very large spatial areas, and relatively southern latitudes in terms of cycling species. We analyzed sage-grouse lek counts and annual hunter harvest indices from 1982 to 2007. We show that greater sage-grouse, currently listed as warranted but precluded under the US Endangered Species Act, and cottontails have highly correlated cycles (r = 0.77). We explore possible mechanistic hypotheses to explain the synchronous population cycles. Our research highlights the importance of control populations in both adaptive management and impact studies. Furthermore, we demonstrate the functional value of these indices (lek counts and hunter harvest) for tracking broad-scale fluctuations in the species. This level of highly correlated long-term cycling has not previously been documented between two non-related species, over a long time-series, very large spatial scale, and within more southern latitudes.

  20. Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis.

    PubMed

    Kröger, Nicolaus; Zabelina, Tatjana; Schieder, Heike; Panse, Jens; Ayuk, Francis; Stute, Norbert; Fehse, Natalja; Waschke, Olga; Fehse, Boris; Kvasnicka, Hans Michael; Thiele, Jürgen; Zander, Axel

    2005-03-01

    A prospective pilot study was performed to evaluate the effect of reduced-intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32-63). No primary graft failure occurred. The median time until leucocyte (>1.0 x 10(9)/l) and platelet (>20 x 10(9)/l) engraftment was 16 (range, 11-26) and 23 d (range, 9-139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft-versus-host disease (GvHD) grades II-IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment-related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0-32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow-up of 22 months (range, 4-59), the 3-year estimated overall and disease-free survival was 84% (95% CI: 67-100%).

  1. Risk Factors for Steroid-Refractory Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation from Matched Related or Unrelated Donors.

    PubMed

    Calmettes, Claire; Vigouroux, Stéphane; Labopin, Myriam; Tabrizi, Reza; Turlure, Pascal; Lafarge, Xavier; Marit, Gérald; Pigneux, Arnaud; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Mohr, Catherine; Lascaux, Axelle; Dumas, Pierre-Yves; Dimicoli-Salazar, Sophie; Saint-Lézer, Arnaud; Milpied, Noël

    2015-05-01

    We performed a retrospective study to identify pretransplantation risk factors for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after allogeneic stem cell transplantation from matched donors in 630 adult patients who underwent transplantation at our center between 2000 and 2012. The cumulative incidence (CI) of SR aGVHD was 11.3% ± 2.3%. The identified independent risk factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte globulin (HR, 2.02; P = .005). Three risk groups were defined according to the presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5% ± 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% ± 1.6% in the intermediate-risk group (1 risk factor, n = 323), and 19.3% ± 2.9% in the high-risk group (2 or 3 risk factors, n = 192). Our study suggests that pretransplantation characteristics might help identify patients at high risk for SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in those patients.

  2. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse.

    PubMed

    Imahashi, Nobuhiko; Ohashi, Haruhiko; Terakura, Seitaro; Miyao, Kotaro; Sakemura, Reona; Kato, Tomonori; Sawa, Masashi; Yokohata, Emi; Kurahashi, Shingo; Ozawa, Yukiyasu; Nishida, Tetsuya; Kiyoi, Hitoshi; Watamoto, Koichi; Kohno, Akio; Kasai, Masanobu; Kato, Chiaki; Iida, Hiroatsu; Naoe, Tomoki; Miyamura, Koichi; Murata, Makoto

    2015-07-01

    Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.

  3. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI.

    PubMed

    Cluzeau, T; Lambert, J; Raus, N; Dessaux, K; Absi, L; Delbos, F; Devys, A; De Matteis, M; Dubois, V; Filloux, M; Fort, M; Hau, F; Jollet, I; Labalette, M; Masson, D; Mercier, B; Pedron, B; Perrier, P; Picard, C; Quainon, F; Ramounau-Pigot, A; Renac, V; Van Endert, P; Charron, D; Peffault de la Tour, R; Taupin, J L; Loiseau, P

    2016-05-01

    Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort. PMID:26855158

  4. Thymic function recovery after unrelated donor cord blood or T-cell depleted HLA-haploidentical stem cell transplantation correlates with leukemia relapse

    PubMed Central

    Clave, Emmanuel; Lisini, Daniela; Douay, Corinne; Giorgiani, Giovanna; Busson, Marc; Zecca, Marco; Moretta, Francesca; Acquafredda, Gloria; Brescia, Letizia P.; Locatelli, Franco; Toubert, Antoine

    2013-01-01

    Use of alternative donors/sources of hematopoietic stem cells (HSC), such as cord blood (CB) or HLA-haploidentical (Haplo)-related donors, is associated with a significant delay in immune reconstitution after transplantation. Long-term T-cell immune reconstitution largely relies on the generation of new T cells in the recipient thymus, which can be evaluated through signal joint (sj) and beta T-cell-Receptor Excision Circles (TREC) quantification. We studied two groups of 33 and 24 children receiving, respectively, HSC Transplantation (HSCT) from an HLA-haploidentical family donor or an unrelated CB donor, for both malignant (46) and non-malignant disorders (11). Relative and absolute sj and beta-TREC values indicated comparable thymic function reconstitution at 3 and 6 months after the allograft in both groups. Compared to children with non-malignant disorders, those with hematological malignancies had significantly lower pre-transplantation TREC counts. Patients who relapsed after HSCT had a significantly less efficient thymic function both before and 6 months after HSCT with especially low beta-TREC values, this finding suggesting an impact of early intra-thymic T-cell differentiation on the occurrence of leukemia relapse. PMID:23459761

  5. Nonlinear dynamics in cardiac conduction

    NASA Technical Reports Server (NTRS)

    Kaplan, D. T.; Smith, J. M.; Saxberg, B. E.; Cohen, R. J.

    1988-01-01

    Electrical conduction in the heart shows many phenomena familiar from nonlinear dynamics. Among these phenomena are multiple basins of attraction, phase locking, and perhaps period-doubling bifurcations and chaos. We describe a simple cellular-automation model of electrical conduction which simulates normal conduction patterns in the heart as well as a wide range of disturbances of heart rhythm. In addition, we review the application of percolation theory to the analysis of the development of complex, self-sustaining conduction patterns.

  6. Maternal smoking during pregnancy and offspring conduct problems: Evidence from three independent genetically-sensitive research designs

    PubMed Central

    Gaysina, Darya; Fergusson, David M.; Leve, Leslie D.; Horwood, John; Reiss, David; Shaw, Daniel S.; Elam, Kit K.; Natsuaki, Misaki N.; Neiderhiser, Jenae M.; Harold, Gordon T.

    2013-01-01

    Context A number of studies report an association between maternal smoking during pregnancy and offspring conduct disorder. However, past research evidences difficulty disaggregating prenatal environmental from genetic and postnatal environmental influences. Objective To examine the relationship between maternal smoking during pregnancy and offspring conduct problems among children reared by genetically-related and genetically-unrelated mothers. Design, Setting and Participants Three studies employing distinct but complementary research designs were utilized: The Christchurch Health and Development Study (a longitudinal cohort study that includes biological and adopted children), the Early Growth and Development Study (a longitudinal adoption at birth study), and the Cardiff IVF Study (genetically-related and -unrelated families; an adoption at conception study). Maternal smoking during pregnancy was measured as the average number of cigarettes/day (0, 1–9 or 10+) smoked during pregnancy. A number of possible covariates (child gender, ethnicity, birth weight, breast feeding, maternal age at birth, maternal education, family SES, family breakdown, placement age, and parenting practices) were controlled in the analyses. Main Outcome Measure Child conduct problems (age 4–10 years) reported by parents and/or teachers using the Rutter and Conners behaviour scales, the Child Behavior Checklist and Children's Behavior Questionnaire, and the Strengths and Difficulties Questionnaire. Results A significant association between maternal smoking during pregnancy and child conduct problems was observed among children reared by genetically-related and genetically-unrelated mothers. Results from a meta-analysis affirmed this pattern of findings across pooled study samples. Conclusions Findings across the three studies using a complement of genetically-sensitive research designs suggest smoking during pregnancy is a prenatal risk factor for offspring conduct problems, when

  7. Rapid prototype extruded conductive pathways

    DOEpatents

    Bobbitt, III, John T.

    2016-06-21

    A process of producing electrically conductive pathways within additively manufactured parts and similar parts made by plastic extrusion nozzles. The process allows for a three-dimensional part having both conductive and non-conductive portions and allows for such parts to be manufactured in a single production step.

  8. A Simple Audio Conductivity Device.

    ERIC Educational Resources Information Center

    Berenato, Gregory; Maynard, David F.

    1997-01-01

    Describes a simple audio conductivity device built to address the problem of the lack of sensitivity needed to measure small differences in conductivity in crude conductivity devices. Uses a 9-V battery as a power supply and allows the relative resistance differences between substances to be detected by the frequency of its audible tones. Presents…

  9. Draft Genome Sequences of the Two Unrelated Macrolide-Resistant Corynebacterium argentoratense Strains CNM 463/05 and CNM 601/08, Isolated from Patients in the University Hospital of León, Spain

    PubMed Central

    Soriano, Francisco; Acedo, Alberto; Hernandez, Marta; Tauch, Andreas

    2015-01-01

    Corynebacterium argentoratense has been associated mainly with infections in the human respiratory tract. Genome sequencing of two unrelated clinical macrolide-resistant strains, CNM 463/05 and CNM 601/08, revealed the presence of the antibiotic resistance gene erm(X) allocated to a specific genomic region with 100% similarity to the widely distributed transposable element Tn5432. PMID:26159536

  10. Genome-Wide Copy Number Variation Analysis in Extended Families and Unrelated Individuals Characterized for Musical Aptitude and Creativity in Music

    PubMed Central

    Oikkonen, Jaana; Buck, Gemma; Blancher, Christine; Raijas, Pirre; Karma, Kai; Lähdesmäki, Harri; Järvelä, Irma

    2013-01-01

    Music perception and practice represent complex cognitive functions of the human brain. Recently, evidence for the molecular genetic background of music related phenotypes has been obtained. In order to further elucidate the molecular background of musical phenotypes we analyzed genome wide copy number variations (CNVs) in five extended pedigrees and in 172 unrelated subjects characterized for musical aptitude and creative functions in music. Musical aptitude was defined by combination of the scores of three music tests (COMB scores): auditory structuring ability, Seashores test for pitch and for time. Data on creativity in music (herein composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Several CNVRs containing genes that affect neurodevelopment, learning and memory were detected. A deletion at 5q31.1 covering the protocadherin-α gene cluster (Pcdha 1-9) was found co-segregating with low music test scores (COMB) in both sample sets. Pcdha is involved in neural migration, differentiation and synaptogenesis. Creativity in music was found to co-segregate with a duplication covering glucose mutarotase gene (GALM) at 2p22. GALM has influence on serotonin release and membrane trafficking of the human serotonin transporter. Interestingly, genes related to serotonergic systems have been shown to associate not only with psychiatric disorders but also with creativity and music perception. Both, Pcdha and GALM, are related to the serotonergic systems influencing cognitive and motor functions, important for music perception and practice. Finally, a 1.3 Mb duplication was identified in a subject with low COMB scores in the region previously linked with absolute pitch (AP) at 8q24. No differences in the CNV burden was detected among the high/low music test scores or creative/non-creative groups. In summary, CNVs and genes found in this study are related to cognitive functions. Our result suggests new candidate genes for music

  11. Degradation of λ-carrageenan by Pseudoalteromonas carrageenovora λ-carrageenase: a new family of glycoside hydrolases unrelated to κ- and ι-carrageenases

    PubMed Central

    Guibet, Marion; Colin, Sébastien; Barbeyron, Tristan; Genicot, Sabine; Kloareg, Bernard; Michel, Gurvan; Helbert, William

    2007-01-01

    Carrageenans are sulfated galactans found in the cell walls of red seaweeds. They are classified according to the number and the position of sulfate ester groups. λ-Carrageenan is the most sulfated carrageenan and carries at least three sulfates per disaccharide unit. The sole known depolymerizing enzyme of λ-carrageenan, the λ-carrageenase from Pseudoalteromonas carrageenovora, has been purified, cloned and sequenced. Sequence analyses have revealed that the λ-carrageenase, referred to as CglA, is the first member of a new family of GHs (glycoside hydrolases), which is unrelated to families GH16, that contains κ-carrageenases, and GH82, that contains ι-carrageenases. This large enzyme (105 kDa) features a low-complexity region, suggesting the presence of a linker connecting at least two independent modules. The N-terminal region is predicted to fold as a β-propeller. The main degradation products have been purified and characterized as neo-λ-carratetraose [DP (degree of polymerization) 4] and neo-λ-carrahexaose (DP6), indicating that CglA hydrolyses the β-(1→4) linkage of λ-carrageenan. LC-MALLS (liquid chromatography-multi-angle laser light scattering) and 1H-NMR monitoring of the enzymatic degradation of λ-carrageenan indicate that CglA proceeds according to an endolytic mode of action and a mechanism of inversion of the anomeric configuration. Using 2-aminoacridone-labelled neo-λ-carrabiose oligosaccharides, in the present study we demonstrate that the active site of CglA comprises at least 8 subsites (−4 to +4) and that a DP6 oligosaccharide binds in the subsites −4 to +2 and can be hydrolysed into DP4 and DP2. PMID:17269933

  12. Genome-wide copy number variation analysis in extended families and unrelated individuals characterized for musical aptitude and creativity in music.

    PubMed

    Ukkola-Vuoti, Liisa; Kanduri, Chakravarthi; Oikkonen, Jaana; Buck, Gemma; Blancher, Christine; Raijas, Pirre; Karma, Kai; Lähdesmäki, Harri; Järvelä, Irma

    2013-01-01

    Music perception and practice represent complex cognitive functions of the human brain. Recently, evidence for the molecular genetic background of music related phenotypes has been obtained. In order to further elucidate the molecular background of musical phenotypes we analyzed genome wide copy number variations (CNVs) in five extended pedigrees and in 172 unrelated subjects characterized for musical aptitude and creative functions in music. Musical aptitude was defined by combination of the scores of three music tests (COMB scores): auditory structuring ability, Seashores test for pitch and for time. Data on creativity in music (herein composing, improvising and/or arranging music) was surveyed using a web-based questionnaire.Several CNVRs containing genes that affect neurodevelopment, learning and memory were detected. A deletion at 5q31.1 covering the protocadherin-α gene cluster (Pcdha 1-9) was found co-segregating with low music test scores (COMB) in both sample sets. Pcdha is involved in neural migration, differentiation and synaptogenesis. Creativity in music was found to co-segregate with a duplication covering glucose mutarotase gene (GALM) at 2p22. GALM has influence on serotonin release and membrane trafficking of the human serotonin transporter. Interestingly, genes related to serotonergic systems have been shown to associate not only with psychiatric disorders but also with creativity and music perception. Both, Pcdha and GALM, are related to the serotonergic systems influencing cognitive and motor functions, important for music perception and practice. Finally, a 1.3 Mb duplication was identified in a subject with low COMB scores in the region previously linked with absolute pitch (AP) at 8q24. No differences in the CNV burden was detected among the high/low music test scores or creative/non-creative groups. In summary, CNVs and genes found in this study are related to cognitive functions. Our result suggests new candidate genes for music perception

  13. High-Resolution Match Rate of 7/8 and 9/10 or Better for the Be The Match Unrelated Donor Registry.

    PubMed

    Buck, Kelly; Wadsworth, Kim; Setterholm, Michelle; Maiers, Martin; Confer, Dennis; Hartzman, Robert; Schmidt, Alexander; Yang, Soo Young; Dehn, Jason

    2016-04-01

    Estimation of the National Marrow Donor Program's Be The Match Registry 8/8 (HLA-A, -B, -C, and -DRB1) high-resolution (HR) unrelated donor (URD) match rate was determined in a prior study for each of the 4 most frequent patient race/ethnic groups in the United States: white (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American (AFA). For patients without an 8/8 HLA-matched URD, a 7/8 match, with a single allele or antigen mismatch, is often accepted by many transplant centers. A follow-up study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Of previously HR tested URDs in the Be The Match Registry, 1344 were randomly selected and treated as pseudo-patients where HR testing was performed to identify a 7/8-matched URD; 98% of WH and over 80% of non-WH race/ethnic groups (HIS, API, and AFA) had at least a 7/8 match identified. In most cases after first testing to identify an 8/8-matched URD, a 7/8-matched URD was identified after typing just 1 URD. Extending criteria to identify a 9/10 match (included HLA-DQB1) showed the 9/10 absolute match rate decreased between 14% and 21% from the 7/8 match rate for the non-WH groups. This study provides a baseline 7/8 and 9/10 or better HLA match rate that can be further supplemented using the additional worldwide URD inventory. URD match rate information can equip centers in clinical planning and the education of patients seeking a life-saving therapy.

  14. Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors

    PubMed Central

    Arrieta-Bolaños, Esteban; Mayor, Neema P.; Marsh, Steven G.E.; Madrigal, J. Alejandro; Apperley, Jane F.; Kirkland, Keiren; Mackinnon, Stephen; Marks, David I.; McQuaker, Grant; Perry, Julia; Potter, Michael N.; Russell, Nigel H.; Thomson, Kirsty; Shaw, Bronwen E.

    2016-01-01

    Transforming growth factor β-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, ‘p001’, showed significantly reduced overall survival (5-year overall survival 30.7% for p001/p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year non-relapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04–2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06–2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor β-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor β-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms. PMID:26611472

  15. Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies.

    PubMed

    Corrons, J L; Alvarez, R; Pujades, A; Zarza, R; Oliva, E; Lasheras, G; Callis, M; Ribes, A; Gelbart, T; Beutler, E

    2001-02-01

    In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxoprolinuria, but without neurological manifestations. The family study revealed GSH-S activity in both parents to be around half the normal level, a finding consistent with the presumed autosomal recessive mode of inheritance of this enzymopathy. Two cases exhibited a well-compensated haemolytic syndrome without anaemia or splenomegaly at steady state. One of these cases was diagnosed after an episode of acute haemolytic anaemia after fava bean ingestion. The remaining patient suffered from moderate to severe chronic non-spherocytic haemolytic anaemia and splenomegaly, and required occasional blood transfusion for a haemolytic crisis associated with drug ingestion. In this patient, the anaemia was corrected by splenectomy. In addition to GSH-S, a panel of 16 other RBC enzyme activities was also studied in all the patients. Hexokinase, aldolase, glucose-6-phosphate dehydrogenase and pyruvate kinase activities all increased; these increases were to be expected, given the rise in the number of circulating reticulocytes. In two patients, the incubation of RBCs with hydrogen peroxide revealed an enhanced production of malonyldialdehyde. DNA analysis showed a homozygous state for 656 A-->G mutation in patients 2 and 3. The GSH-S gene of patient 1, studied elsewhere, revealed an 808 T-->C. The GSH-S gene of patient 4 was not available for study. The present study demonstrates that GSH-S deficiency is also present in Spain and further supports the molecular and clinical heterogeneity of this enzymopathy PMID:11167850

  16. Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature.

    PubMed

    Ozbek, M Nuri; Senée, Valérie; Aydemir, Sehnaz; Kotan, L Damla; Mungan, Neslihan O; Yuksel, Bilgin; Julier, Cécile; Topaloglu, A Kemal

    2010-06-01

    Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3-W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype. PMID:20202148

  17. Comparison of outcomes of hematopoietic stem cell transplant without chemotherapy conditioning using matched sibling and unrelated donors for treatment of SCID

    PubMed Central

    Dvorak, Christopher C.; Hassan, Amel; Slatter, Mary A.; Hönig, Manfred; Lankester, Arjan C.; Buckley, Rebecca H.; Pulsipher, Michael A.; Davis, Jeffrey H.; Güngör, Tayfun; Gabriel, Melissa; Bleesing, Jacob H.; Bunin, Nancy; Sedlacek, Petr; Connelly, James A.; Crawford, David F.; Notarangelo, Luigi D.; Pai, Sung-Yun; Hassid, Jake; Veys, Paul; Gennery, Andrew R.; Cowan, Morton J.

    2014-01-01

    Background Patients with severe combined immunodeficiency disease (SCID) who have matched sibling donors (MSD) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. Objective To determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URD), either from volunteer adults or umbilical cord blood, are comparable to those from matched sibling donors (MSD). Methods A multicenter survey of SCID transplant centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT, from either URDs (n = 37) or MSDs (n = 66). Results Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment, compared to 97% for MSDs, however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively), compared to MSD recipients (92% and 89%, respectively; P <0.01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year OS (100%) to MSD recipients. The incidences of Grade II-IV acute and chronic GVHD were higher in URD (50% and 39%, respectively), compared to MSD recipients (22% and 5%, respectively; P <0.01 for both). In the surviving patients, there was no difference in T-cell reconstitution at last follow-up between the URD recipients and MSD recipients, however MSD recipients were more likely to achieve B-cell reconstitution (72% vs. 17%; P <0.001). Conclusion Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to MSD recipients, and reconstitution rates are adequate. However, only a minority will develop myeloid and B cell reconstitution and attention must be paid to GVHD prophylaxis. This approach may be safer in children ineligible for intense regimens to spare potential complications of chemotherapy. PMID:25109802

  18. A Comparison of the Cheater Detection and the Unrelated Question Models: A Randomized Response Survey on Physical and Cognitive Doping in Recreational Triathletes

    PubMed Central

    Schröter, Hannes; Studzinski, Beatrix; Dietz, Pavel; Ulrich, Rolf; Striegel, Heiko; Simon, Perikles

    2016-01-01

    Purpose This study assessed the prevalence of physical and cognitive doping in recreational triathletes with two different randomized response models, that is, the Cheater Detection Model (CDM) and the Unrelated Question Model (UQM). Since both models have been employed in assessing doping, the major objective of this study was to investigate whether the estimates of these two models converge. Material and Methods An anonymous questionnaire was distributed to 2,967 athletes at two triathlon events (Frankfurt and Wiesbaden, Germany). Doping behavior was assessed either with the CDM (Frankfurt sample, one Wiesbaden subsample) or the UQM (one Wiesbaden subsample). A generalized likelihood-ratio test was employed to check whether the prevalence estimates differed significantly between models. In addition, we compared the prevalence rates of the present survey with those of a previous study on a comparable sample. Results After exclusion of incomplete questionnaires and outliers, the data of 2,017 athletes entered the final data analysis. Twelve-month prevalence for physical doping ranged from 4% (Wiesbaden, CDM and UQM) to 12% (Frankfurt CDM), and for cognitive doping from 1% (Wiesbaden, CDM) to 9% (Frankfurt CDM). The generalized likelihood-ratio test indicated no differences in prevalence rates between the two methods. Furthermore, there were no significant differences in prevalences between the present (undertaken in 2014) and the previous survey (undertaken in 2011), although the estimates tended to be smaller in the present survey. Discussion The results suggest that the two models can provide converging prevalence estimates. The high rate of cheaters estimated by the CDM, however, suggests that the present results must be seen as a lower bound and that the true prevalence of doping might be considerably higher. PMID:27218830

  19. Expression, in cartilage, of a 7-amino-acid deletion in type II collagen from two unrelated individuals with Kniest dysplasia.

    PubMed Central

    Bogaert, R.; Wilkin, D.; Wilcox, W. R.; Lachman, R.; Rimoin, D.; Cohn, D. H.; Eyre, D. R.

    1994-01-01

    Kniest dysplasia is a heritable chondrodysplasia that severely affects skeletal growth. Recent evidence suggests that the etiology is based on mutations in COL2A1, the gene for collagen type II. We report the detection and partial characterization of an identical defect in type II collagen in two unrelated patients with Kniest dysplasia. Analysis of cyanogen bromide (CB)-digested cartilage samples from both probands by SDS-PAGE revealed an abnormal band for peptide alpha 1(II)CB12. The peptide was purified and digested with endoproteinase Asp-N. Fragments unique to the Kniest tissues were identified by reverse-phase high-pressure liquid chromatography and by sequence analysis. The results established a deletion of amino acids 102-108 of the alpha 1(II) triple-helical domain, which disrupted the (gly-X-Y)n repeat needed for helix formation. This was confirmed by sequence analysis of DNA amplified from both probands, revealing the molecular basis to be a single nucleotide mutation at a CpG dinucleotide (GCG-->GTG) in the codon for alanine 102. The mutation created a new splice donor site, which would account for the absence of the last seven amino acids from the 3' end of exon 12 in alpha 1(II)CB12. Light and electron micrographs of the probands' cartilage showed the perilacunar foamy matrix ("Swiss cheese") characteristic of Kniest dysplasia and chondrocytes containing dilated rough endoplasmic reticulum, which earlier studies had shown were filled with type II procollagen. These two cases strengthen the concept that Kniest dysplasia is based on mutations of COL2A1 and belongs within the broad spectrum of chondrodysplasias caused by type II collagenopathies. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 7 Figure 8 PMID:7977371

  20. Molecular analysis of three Ljungan virus isolates reveals a new, close-to-root lineage of the Picornaviridae with a cluster of two unrelated 2A proteins.

    PubMed

    Johansson, Susanne; Niklasson, Bo; Maizel, Jacob; Gorbalenya, Alexander E; Lindberg, A Michael

    2002-09-01

    Ljungan virus (LV) is a suspected human pathogen recently isolated from bank voles (Clethrionomys glareolus). In the present study, it is revealed through comparative sequence analysis that three newly determined Swedish LV genomes are closely related and possess a deviant picornavirus-like organization: 5' untranslated region-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' untranslated region. The LV genomes and the polyproteins encoded by them exhibit several exceptional features, such as the absence of a predicted maturation cleavage of VP0, a conserved sequence determinant in VP0 that is typically found in VP1 of other picornaviruses, and a cluster of two unrelated 2A proteins. The 2A1 protein is related to the 2A protein of cardio-, erbo-, tescho-, and aphthoviruses, and the 2A2 protein is related to the 2A protein of parechoviruses, kobuviruses, and avian encephalomyelitis virus. The unprecedented association of two structurally different 2A proteins is a feature never previously observed among picornaviruses and implies that their functions are not mutually exclusive. Secondary polyprotein processing of the LV polyprotein is mediated by proteinase 3C (3C(pro)) possessing canonical affinity to Glu and Gln at the P1 position and small amino acid residues at the P1' position. In addition, LV 3C(pro) appears to have unique substrate specificity to Asn, Gln, and Asp and to bulky hydrophobic residues at the P2 and P4 positions, respectively. Phylogenetic analysis suggests that LVs form a separate division, which, together with the Parechovirus genus, has branched off the picornavirus tree most closely to its root. The presence of two 2A proteins indicates that some contemporary picornaviruses with a single 2A may have evolved from the ancestral multi-2A picornavirus.

  1. Electronic conduction in liquid boron

    NASA Astrophysics Data System (ADS)

    Glorieux, B.; Saboungi, M. L.; Enderby, J. E.

    2001-10-01

    The electrical conductivity of levitated liquid elemental boron was measured near the melting point using a contactless electrical conductivity technique. A phase change is clearly detected in the course of laser heating of a 2 mm diameter boron sphere levitated aerodynamically. The value obtained for the electrical conductivity sets liquid boron among the liquid semiconductors and establishes that the semiconducting behavior survives the melting process contradicting an earlier report that a semiconductor-to-metal transition occurs.

  2. Temperature dependence of conductivity measurement for conducting polymer

    NASA Astrophysics Data System (ADS)

    Gutierrez, Leandro; Duran, Jesus; Isah, Anne; Albers, Patrick; McDougall, Michael; Wang, Weining

    2014-03-01

    Conducting polymer-based solar cells are the newest generation solar cells. While research on this area has been progressing, the efficiency is still low because certain important parameters of the solar cell are still not well understood. It is of interest to study the temperature dependence of the solar cell parameters, such as conductivity of the polymer, open circuit voltage, and reverse saturation current to gain a better understanding on the solar cells. In this work, we report our temperature dependence of conductivity measurement using our in-house temperature-varying apparatus. In this project, we designed and built a temperature varying apparatus using a thermoelectric cooler module which gives enough temperature range as we need and costs much less than a cryostat. The set-up of the apparatus will be discussed. Temperature dependence of conductivity measurements for PEDOT:PSS films with different room-temperature conductivity will be compared and discussed. NJSGC-NASA Fellowship grant

  3. Thermal conductivity of boron carbides

    NASA Technical Reports Server (NTRS)

    Wood, C.; Emin, D.; Gray, P. E.

    1985-01-01

    Knowledge of the thermal conductivity of boron carbide is necessary to evaluate its potential for high-temperature thermoelectric energy conversion applications. Measurements have been conducted of the thermal diffusivity of hot-pressed boron carbide BxC samples as a function of composition (x in the range from 4 to 9), temperature (300-1700 K), and temperature cycling. These data, in concert with density and specific-heat data, yield the thermal conductivities of these materials. The results are discussed in terms of a structural model that has been previously advanced to explain the electronic transport data. Some novel mechanisms for thermal conduction are briefly discussed.

  4. Thermal conductivity of supercooled water.

    PubMed

    Biddle, John W; Holten, Vincent; Sengers, Jan V; Anisimov, Mikhail A

    2013-04-01

    The heat capacity of supercooled water, measured down to -37°C, shows an anomalous increase as temperature decreases. The thermal diffusivity, i.e., the ratio of the thermal conductivity and the heat capacity per unit volume, shows a decrease. These anomalies may be associated with a hypothesized liquid-liquid critical point in supercooled water below the line of homogeneous nucleation. However, while the thermal conductivity is known to diverge at the vapor-liquid critical point due to critical density fluctuations, the thermal conductivity of supercooled water, calculated as the product of thermal diffusivity and heat capacity, does not show any sign of such an anomaly. We have used mode-coupling theory to investigate the possible effect of critical fluctuations on the thermal conductivity of supercooled water and found that indeed any critical thermal-conductivity enhancement would be too small to be measurable at experimentally accessible temperatures. Moreover, the behavior of thermal conductivity can be explained by the observed anomalies of the thermodynamic properties. In particular, we show that thermal conductivity should go through a minimum when temperature is decreased, as Kumar and Stanley observed in the TIP5P model of water. We discuss physical reasons for the striking difference between the behavior of thermal conductivity in water near the vapor-liquid and liquid-liquid critical points.

  5. Electrically conductive anodized aluminum coatings

    NASA Technical Reports Server (NTRS)

    Alwitt, Robert S. (Inventor); Liu, Yanming (Inventor)

    2001-01-01

    A process for producing anodized aluminum with enhanced electrical conductivity, comprising anodic oxidation of aluminum alloy substrate, electrolytic deposition of a small amount of metal into the pores of the anodized aluminum, and electrolytic anodic deposition of an electrically conductive oxide, including manganese dioxide, into the pores containing the metal deposit; and the product produced by the process.

  6. Bone-Conduction ABR Tests.

    ERIC Educational Resources Information Center

    Cone-Wesson, Barbara

    1995-01-01

    This article discusses the accuracy of bone-conduction auditory brainstem response (BC-ABR) tests to determine the presence and severity of conductive hearing impairment. It provides warnings about technical pitfalls and recommends incorporating BC-ABR protocols for routine clinical use. It concludes that the method allows estimating cochlear…

  7. Skin-conductance orienting response in chronic schizophrenics: the role of neuroleptics.

    PubMed

    Spohn, H E; Coyne, L; Wilson, J K; Hayes, K

    1989-11-01

    The primary aim of this study was to determine whether there is an association between neuroleptic treatment and skin-conductance orienting response (SCOR) nonresponding in chronic schizophrenics. In a design adapted to this purpose, we were unable to demonstrate a relationship between neuroleptics and nonresponding. Although inability to prove the null hypothesis precludes a claim that neuroleptic treatment and SCOR nonresponding are unrelated, internal evidence and prior studies strongly suggest that such a dissociation exists in most chronic schizophrenic nonresponders. We also found stable nonspecific and toxic skin conductance activity differences between SCOR "responders" and "nonresponders" on three occasions of testing. We interpret our results as bearing on state and trait issues in chronic schizophrenics.

  8. Conductive polymer-based material

    SciTech Connect

    McDonald, William F.; Koren, Amy B.; Dourado, Sunil K.; Dulebohn, Joel I.; Hanchar, Robert J.

    2007-04-17

    Disclosed are polymer-based coatings and materials comprising (i) a polymeric composition including a polymer having side chains along a backbone forming the polymer, at least two of the side chains being substituted with a heteroatom selected from oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and (ii) a plurality of metal species distributed within the polymer. At least a portion of the heteroatoms may form part of a chelation complex with some or all of the metal species. In many embodiments, the metal species are present in a sufficient concentration to provide a conductive material, e.g., as a conductive coating on a substrate. The conductive materials may be useful as the thin film conducting or semi-conducting layers in organic electronic devices such as organic electroluminescent devices and organic thin film transistors.

  9. Conductivity-limiting bipolar thermal conductivity in semiconductors

    PubMed Central

    Wang, Shanyu; Yang, Jiong; Toll, Trevor; Yang, Jihui; Zhang, Wenqing; Tang, Xinfeng

    2015-01-01

    Intriguing experimental results raised the question about the fundamental mechanisms governing the electron-hole coupling induced bipolar thermal conduction in semiconductors. Our combined theoretical analysis and experimental measurements show that in semiconductors bipolar thermal transport is in general a “conductivity-limiting” phenomenon, and it is thus controlled by the carrier mobility ratio and by the minority carrier partial electrical conductivity for the intrinsic and extrinsic cases, respectively. Our numerical method quantifies the role of electronic band structure and carrier scattering mechanisms. We have successfully demonstrated bipolar thermal conductivity reduction in doped semiconductors via electronic band structure modulation and/or preferential minority carrier scatterings. We expect this study to be beneficial to the current interests in optimizing thermoelectric properties of narrow gap semiconductors. PMID:25970560

  10. Conductivity-limiting bipolar thermal conductivity in semiconductors.

    PubMed

    Wang, Shanyu; Yang, Jiong; Toll, Trevor; Yang, Jihui; Zhang, Wenqing; Tang, Xinfeng

    2015-01-01

    Intriguing experimental results raised the question about the fundamental mechanisms governing the electron-hole coupling induced bipolar thermal conduction in semiconductors. Our combined theoretical analysis and experimental measurements show that in semiconductors bipolar thermal transport is in general a "conductivity-limiting" phenomenon, and it is thus controlled by the carrier mobility ratio and by the minority carrier partial electrical conductivity for the intrinsic and extrinsic cases, respectively. Our numerical method quantifies the role of electronic band structure and carrier scattering mechanisms. We have successfully demonstrated bipolar thermal conductivity reduction in doped semiconductors via electronic band structure modulation and/or preferential minority carrier scatterings. We expect this study to be beneficial to the current interests in optimizing thermoelectric properties of narrow gap semiconductors. PMID:25970560

  11. Calibration-free electrical conductivity measurements for highly conductive slags

    SciTech Connect

    MACDONALD,CHRISTOPHER J.; GAO,HUANG; PAL,UDAY B.; VAN DEN AVYLE,JAMES A.; MELGAARD,DAVID K.

    2000-05-01

    This research involves the measurement of the electrical conductivity (K) for the ESR (electroslag remelting) slag (60 wt.% CaF{sub 2} - 20 wt.% CaO - 20 wt.% Al{sub 2}O{sub 3}) used in the decontamination of radioactive stainless steel. The electrical conductivity is measured with an improved high-accuracy-height-differential technique that requires no calibration. This method consists of making continuous AC impedance measurements over several successive depth increments of the coaxial cylindrical electrodes in the ESR slag. The electrical conductivity is then calculated from the slope of the plot of inverse impedance versus the depth of the electrodes in the slag. The improvements on the existing technique include an increased electrochemical cell geometry and the capability of measuring high precision depth increments and the associated impedances. These improvements allow this technique to be used for measuring the electrical conductivity of highly conductive slags such as the ESR slag. The volatilization rate and the volatile species of the ESR slag measured through thermogravimetric (TG) and mass spectroscopy analysis, respectively, reveal that the ESR slag composition essentially remains the same throughout the electrical conductivity experiments.

  12. Effects of compatability on the conductivity of conducting polymer blends

    SciTech Connect

    Liu, Mingjun; Nowak, C.K.; Gregory, R.V.

    1995-12-01

    The electrical conductivity of chemically synthesized polyaniline (PANI) blends with nylon 6,6 and polystyrene was measured. The conductivities of the top and bottom of the films cast from blend solutions were found to differ. This effect was most pronounced at low percent loadings of PANI. The maximum difference in conductivity between two sides of the same film was found to be five orders of magnitude in the case of a 5% PANI blend with polystyrene. In this case the conductive polymer appears to be rich on one side of the film rather than more homogeneously dispersed on both sides. SEM provides evidence for the formation of a percolation cluster on one side of the film which is most notable in polystyrene blends. X-ray and FTIR indicated that greater interaction between PANI and nylon 6,6 than PANI and polystyrene. It is proposed that the magnitude of the variation in conductivity between the two sides of the film depends on the compatibility of the conducting and insulating host polymers.

  13. Edge conduction in vacuum glazing

    SciTech Connect

    Simko, T.M.; Collins, R.E.; Beck, F.A.; Arasteh, D.

    1995-03-01

    Vacuum glazing is a form of low-conductance double glazing using in internal vacuum between the two glass sheets to eliminate heat transport by gas conduction and convection. An array of small support pillars separates the sheets; fused solder glass forms the edge seal. Heat transfer through the glazing occurs by radiation across the vacuum gap, conduction through the support pillars, and conduction through the bonded edge seal. Edge conduction is problematic because it affects stresses in the edge region, leading to possible failure of the glazing; in addition, excessive heat transfer because of thermal bridging in the edge region can lower overall window thermal performance and decrease resistance to condensation. Infrared thermography was used to analyze the thermal performance of prototype vacuum glazings, and, for comparison, atmospheric pressure superwindows. Research focused on mitigating the edge effects of vacuum glazings through the use of insulating trim, recessed edges, and framing materials. Experimentally validated finite-element and finite-difference modeling tools were used for thermal analysis of prototype vacuum glazing units and complete windows. Experimental measurements of edge conduction using infrared imaging were found to be in good agreement with finite-element modeling results for a given set of conditions. Finite-element modeling validates an analytic model developed for edge conduction.

  14. Hydraulic conductivity of compacted zeolites.

    PubMed

    Oren, A Hakan; Ozdamar, Tuğçe

    2013-06-01

    Hydraulic conductivities of compacted zeolites were investigated as a function of compaction water content and zeolite particle size. Initially, the compaction characteristics of zeolites were determined. The compaction test results showed that maximum dry unit weight (γ(dmax)) of fine zeolite was greater than that of granular zeolites. The γ(dmax) of compacted zeolites was between 1.01 and 1.17 Mg m(-3) and optimum water content (w(opt)) was between 38% and 53%. Regardless of zeolite particle size, compacted zeolites had low γ(dmax) and high w(opt) when compared with compacted natural soils. Then, hydraulic conductivity tests were run on compacted zeolites. The hydraulic conductivity values were within the range of 2.0 × 10(-3) cm s(-1) to 1.1 × 10(-7) cm s(-1). Hydraulic conductivity of all compacted zeolites decreased almost 50 times as the water content increased. It is noteworthy that hydraulic conductivity of compacted zeolite was strongly dependent on the zeolite particle size. The hydraulic conductivity decreased almost three orders of magnitude up to 39% fine content; then, it remained almost unchanged beyond 39%. Only one report was found in the literature on the hydraulic conductivity of compacted zeolite, which is in agreement with the findings of this study.

  15. Thermal conductivity of graphene laminate.

    PubMed

    Malekpour, H; Chang, K-H; Chen, J-C; Lu, C-Y; Nika, D L; Novoselov, K S; Balandin, A A

    2014-09-10

    We have investigated thermal conductivity of graphene laminate films deposited on polyethylene terephthalate substrates. Two types of graphene laminate were studied, as deposited and compressed, in order to determine the physical parameters affecting the heat conduction the most. The measurements were performed using the optothermal Raman technique and a set of suspended samples with the graphene laminate thickness from 9 to 44 μm. The thermal conductivity of graphene laminate was found to be in the range from 40 to 90 W/mK at room temperature. It was found unexpectedly that the average size and the alignment of graphene flakes are more important parameters defining the heat conduction than the mass density of the graphene laminate. The thermal conductivity scales up linearly with the average graphene flake size in both uncompressed and compressed laminates. The compressed laminates have higher thermal conductivity for the same average flake size owing to better flake alignment. Coating plastic materials with thin graphene laminate films that have up to 600× higher thermal conductivity than plastics may have important practical implications.

  16. Identical de novo Mutation in the Type 1 Ryanodine Receptor Gene Associated with Fatal, Stress-induced Malignant Hyperthermia in Two Unrelated Families

    PubMed Central

    Groom, Linda; Muldoon, Sheila M.; Tang, Zhen Zhi; Brandom, Barbara W.; Bayarsaikhan, Munkhuu; Bina, Saiid; Lee, Hee-Suk; Qiu, X; Sambuughin, Nyamkhishig; Dirksen, Robert T.

    2011-01-01

    BACKGROUND Mutations in the type I ryanodine receptor gene (RYR1) result in malignant hyperthermia, a pharmacogenetic disorder typically triggered by administration of anesthetics. However, cases of sudden death during exertion, heat challenge, and febrile illness in the absence of triggering drugs have been reported. The underlying causes of such drug-free fatal “awake” episodes are unknown. METHODS De novo R3983C variant in RYR1 was identified in two unrelated children that experienced fatal, nonanesthetic awake episodes associated with febrile illness and heat stress. One of the children also possessed a second novel maternally-inherited D4505H variant located on a separate haplotype. Effects of all possible heterotypic expression conditions on RYR1 sensitivity to caffeine-induced Ca2+ release were determined in expressing RyR1-null myotubes. RESULTS Compared to wild-type RYR1 alone (EC50 = 2.85 ± 0.49 mM), average (±SEM) caffeine sensitivity of Ca2+ release was modestly increased following coexpression with either R3983C (EC50 = 2.00 ± 0.39 mM) or D4505H (EC50 = 1.64 ± 0.24 mM). Remarkably, coexpression of wild-type RYR1 with the double mutant in cis (R3983C-D4505H) produced a significantly stronger sensitization of caffeine-induced Ca2+ release (EC50 = 0.64 ± 0.17 mM) compared to that observed following coexpression of the two variants on separate subunits (EC50 = 1.53 ± 0.18 mM). CONCLUSIONS The R3983C mutation potentiates D4505H-mediated sensitization of caffeine-induced RYR1 Ca2+ release when the mutations are in cis (on the same subunit), but not when present on separate subunits. Nevertheless, coexpression of the two variants on separate subunits still resulted in a ~2-fold increase in caffeine sensitivity, consistent with the observed awake episodes and heat sensitivity. PMID:21918424

  17. Time-space focused intrusion of genetically unrelated arc magmas in the early Paleozoic Ross-Delamerian Orogen (Morozumi Range, Antarctica)

    NASA Astrophysics Data System (ADS)

    Rocchi, S.; Di Vincenzo, G.; Dini, A.; Petrelli, M.; Vezzoni, S.

    2015-09-01

    The growth of continental crust in accretionary orogenic belts takes place through repeated cycles of subduction-accretion of rock units from continental and oceanic magmatic arcs, supra-subduction zone backarcs and forearcs loaded with continent-derived materials. An ancient example relevant to magmatic arc accretion models is represented by the remnants of the Cambrian-Ordovician Ross Orogen in the Morozumi Range, Victoria Land (Antarctica). There, late Neoproterozoic phyllites host an intrusive complex which preserves a remarkably uncommon record of genetically unrelated magma pulses emplaced under a variable stress regime in a short time span: (1) a dominant K-feldspar-phyric granite, (2) fine-grained dioritic stocks and dykes, (3) a peraluminous granite; and (4) a tonalitic-granodioritic dyke swarm. Laserprobe U-Pb zircon dates cluster at late Cambrian times for all these units, yet they carry differential cargoes of relict cores. Unique geochemical-isotopic signatures for both the less evolved magmas (diorite and dyke tonalite) and the most acidic ones (granite and peraluminous granite) indicate that each one of them originated from distinct sources at depth. Additionally, field relationships and chemical evolutionary trends testify for a variety of shallow level open-system processes, such as magma mingling/mixing between diorite and main granite magmas, as well as progressive incorporation of the host schists by the dyke tonalite magma. In summary, crustal growth in the Morozumi intrusive complex was contributed by fresh mantle magma issuing from the metasomatised mantle wedge, while the production of other melts did recycle different crustal portions/layers: the main granite derived from Grenville-age granulitic lower crust; the peraluminous granite from late Proterozoic upper crust, and the tonalite magmas derived from subduction erosion-enriched subarc mantle and evolved by ingestion of local metasedimentary rocks. Overall, the Morozumi intrusive complex

  18. Electrically conductive and thermally conductive materials for electronic packaging

    NASA Astrophysics Data System (ADS)

    Liu, Zongrong

    The aim of this dissertation is to develop electrically or thermally conductive materials that are needed for electronic packaging and microelectronic cooling. These materials are in the form of coatings and are made from pastes. The research work encompasses paste formulation, studying the process of converting a paste to a conductive material, relating the processing conditions to the structure and performance, and evaluating performance attributes that are relevant to the application of these conductive materials. The research has resulted in new information that is valuable to the microelectronic industry. Work on electrically conductive materials emphasizes the development of electrical interconnection materials in the form of air-firable glass-free silver-based electrically conductive thick films, which use the Ti-Al alloy as the binder and are in contrast to conventional films that use glass as the binder. The air-firability, as enabled by minor additions of tin and zinc to the paste, is in contrast to previous glass-free films that are not firable. The recommended firing condition is 930°C in air. The organic vehicle in the paste comprises ethyl cellulose, which undergoes thermal decomposition during burnout of the paste. The ethyl cellulose is dissolved in ether, which facilitates the burnout. Excessive ethyl cellulose hinders the burnout. A higher heating rate results in more residue after burnout. The presence of silver particles facilitates drying and burnout. Firing in air gives lower resistivity than firing in oxygen. Firing in argon gives poor films. Compared to conventional films that use glass as the binder, these films, when appropriately fired, exhibit lower electrical resistivity (2.5 x 10-6 O.cm) and higher scratch resistance. Work on thermally conductive materials addresses thermal interface materials, which are materials placed at the interface between a heat sink and a heat source for the purpose of improving the thermal contact. Heat

  19. Variable conductance heat pipe technology

    NASA Technical Reports Server (NTRS)

    Marcus, B. D.; Edwards, D. K.; Anderson, W. T.

    1973-01-01

    Research and development programs in variable conductance heat pipe technology were conducted. The treatment has been comprehensive, involving theoretical and/or experimental studies in hydrostatics, hydrodynamics, heat transfer into and out of the pipe, fluid selection, and materials compatibility, in addition to the principal subject of variable conductance control techniques. Efforts were not limited to analytical work and laboratory experimentation, but extended to the development, fabrication and test of spacecraft hardware, culminating in the successful flight of the Ames Heat Pipe Experiment on the OAO-C spacecraft.

  20. Thermal Conductances Of Metal Contacts

    NASA Technical Reports Server (NTRS)

    Salerno, L. J.; Kittel, P.; Scherkenbach, F. E.; Spivak, A. L.

    1988-01-01

    Report presents results of measurements of thermal conductances of aluminum and stainless-steel contacts at temperatures from 1.6 to 6.0 K. Measurement apparatus includes gearmotor assembly connected to rocker arm by music wire to load sample pair with forces up to 670 N. Heater placed above upper sample. Germanium resistance thermometers in upper and lower samples measured temperature difference across interface over range of heater powers from 0.1 to 10.0 mW. The thermal conductance calculated from temperature difference. Measurements provide data for prediction of thermal conductances of bolted joints in cryogenic infrared instruments.

  1. Shape memory thermal conduction switch

    NASA Technical Reports Server (NTRS)

    Vaidyanathan, Rajan (Inventor); Krishnan, Vinu (Inventor); Notardonato, William U. (Inventor)

    2010-01-01

    A thermal conduction switch includes a thermally-conductive first member having a first thermal contacting structure for securing the first member as a stationary member to a thermally regulated body or a body requiring thermal regulation. A movable thermally-conductive second member has a second thermal contacting surface. A thermally conductive coupler is interposed between the first member and the second member for thermally coupling the first member to the second member. At least one control spring is coupled between the first member and the second member. The control spring includes a NiTiFe comprising shape memory (SM) material that provides a phase change temperature <273 K, a transformation range <40 K, and a hysteresis of <10 K. A bias spring is between the first member and the second member. At the phase change the switch provides a distance change (displacement) between first and second member by at least 1 mm, such as 2 to 4 mm.

  2. Conducting Grains in Dusty Plasmas

    NASA Astrophysics Data System (ADS)

    Hyde, Truell; Matthews, Lorin; Carmona-Reyes, Jorge

    The existence of dusty plasma environments in space is common, with the dust originating from a variety of sources. Such environments include protostellar and protoplanetary systems during their formation and evolution. In addition, iron rich meteors, which contain remnants of primordial solar system material, are also a source for micron-sized metallic dust particles that interact with the surrounding plasma. Although research has been conducted on nonconducting grains within a complex plasma environment, very little experimental data exists on conducting grains within complex plasmas. This study will compare and contrast the dynamics of non-conducting (Melamine Formaldehyde) and conducting particles (Gold-coated Melamine Formaldehyde particles) immersed in a capacitively coupled RF plasma maintained within a GEC reference cell. The resulting experimental data will be related to the fundamental physics behind the charging mechanism for such micron-size particles.

  3. Psychobiological Basis of Conduct Disorder.

    ERIC Educational Resources Information Center

    Shapiro, Steven K.; Hynd, George W.

    1993-01-01

    Examines psychobiological literature pertaining to conduct disorder (CD), with particular emphasis on how such information can increase understanding of youths representing undersocialized aggressive subtype of CD. Reviews literature from neuroanatomical, biochemical, psychophysiological, and pharmacological arenas. Outlines theoretical framework…

  4. Conductivity of a relativistic plasma

    SciTech Connect

    Braams, B.J.; Karney, C.F.F.

    1989-03-01

    The collision operator for a relativistic plasma is reformulated in terms of an expansion in spherical harmonics. This formulation is used to calculate the electrical conductivity. 13 refs., 1 fig., 1 tab.

  5. Conduction mechanism in boron carbide

    NASA Technical Reports Server (NTRS)

    Wood, C.; Emin, D.

    1984-01-01

    Electrical conductivity, Seebeck-coefficient, and Hall-effect measurements have been made on single-phase boron carbides, B(1-x)C(x), in the compositional range from 0.1 to 0.2 X, and between room temperature and 1273 K. The results indicate that the predominant conduction mechanism is small-polaron hopping between carbon atoms at geometrically inequivalent sites.

  6. Electrical conduction in polymer dielectrics

    NASA Technical Reports Server (NTRS)

    Cotts, D. B.

    1985-01-01

    The use of polymer dielectrics with moderate resistivities could reduce or eliminate problems associated with spacecraft charging. The processes responsible for conduction and the properties of electroactive polymers are reviewed, and correlations drawn between molecular structure and electrical conductivity. These structure-property relationships led to the development of several new electroactive polymer compositions and the identification of several systems that have the requisite thermal, mechanical, environmental and electrical properties for use in spacecraft.

  7. Do dialysate conductivity measurements provide conductivity clearance or ionic dialysance?

    PubMed

    Petitclerc, T

    2006-11-01

    Dialysate conductivity measurements allow on-line estimation of urea clearance during hemodialysis session. Conductivity measurements provide a value of 'conductivity clearance' for some authors, but a value of 'ionic dialysance' for others. This paper aims at explaining which term should be the more appropriate. Clearance is a parameter defined for measuring the power of a mechanism, which aims at 'clearing' a solution by depurating some solutes. In hemodialysis, clearance measures the efficacy of patient's depuration. In contrast, dialysance measures the capability of transferring solutes between blood and dialysate. The conventional definition of dialysance, requiring the absence of convective transfer, should be generalized to the case of the usual presence of ultrafiltration during the hemodialysis session. For a solute (as urea) absent from the dialysate delivered to the dialyzer inlet, the clearance is equal to its dialysance. In order to avoid a dramatic fall in ionic concentrations during hemodialysis treatment, the clearance of ions is reduced by adding these ions in the dialysate and becomes lower than their dialysance. Conductivity measurements provide a value of electrolytes dialysance. Thus the term of 'ionic dialysance' is more appropriate than the term of 'conductivity clearance'. Nevertheless ionic dialysance represents a good estimation of urea clearance.

  8. Thermal conductivity of cane fiberboard

    SciTech Connect

    Leader, D.R.

    1995-05-01

    The thermal conductivity of cane fiberboard was measured in two planes; parallel to the surface and perpendicular to the surface of the manufactured sheet. The information was necessary to better understand the thermal response of a loaded shipping container. The tests demonstrated that the thermal conductivity of cane fiberboard in the plane parallel to the surface of the sheet was nearly twice as great as the conductivity of the same material in a plane perpendicular to the sheet. There was no significant difference in the conductivity in different directions within the plane parallel to the surface, and the presence of glue between layers of fiberboard did not significantly change the conductivity of the assembly. The tests revealed that the thermal conductivity measured in a direction perpendicular to the plane of the surface of a stack of cane fiberboard sheets not bonded together, decreases with an increase in the mean temperature. This was determined to be the result of air gaps between the sheets of fiberboard, and not related to the properties of the material itself

  9. Highly elastic conductive polymeric MEMS

    NASA Astrophysics Data System (ADS)

    Ruhhammer, J.; Zens, M.; Goldschmidtboeing, F.; Seifert, A.; Woias, P.

    2015-02-01

    Polymeric structures with integrated, functional microelectrical mechanical systems (MEMS) elements are increasingly important in various applications such as biomedical systems or wearable smart devices. These applications require highly flexible and elastic polymers with good conductivity, which can be embedded into a matrix that undergoes large deformations. Conductive polydimethylsiloxane (PDMS) is a suitable candidate but is still challenging to fabricate. Conductivity is achieved by filling a nonconductive PDMS matrix with conductive particles. In this work, we present an approach that uses new mixing techniques to fabricate conductive PDMS with different fillers such as carbon black, silver particles, and multiwalled carbon nanotubes. Additionally, the electrical properties of all three composites are examined under continuous mechanical stress. Furthermore, we present a novel, low-cost, simple three-step molding process that transfers a micro patterned silicon master into a polystyrene (PS) polytetrafluoroethylene (PTFE) replica with improved release features. This PS/PTFE mold is used for subsequent structuring of conductive PDMS with high accuracy. The non sticking characteristics enable the fabrication of delicate structures using a very soft PDMS, which is usually hard to release from conventional molds. Moreover, the process can also be applied to polyurethanes and various other material combinations.

  10. Synthesis and characterization of soluble conducting polymers and conducting adhesives

    NASA Astrophysics Data System (ADS)

    Oztemiz, Serhan

    With the demanding nature of the technology today, scientists are looking for new materials in order to decrease the cost, increase the efficiency of the use of the materials, and decrease time-consuming steps in order to increase the speed of production. New materials are being studied to decrease the weight of cars, planes and space vehicles; surface properties are being modified to decrease the drag coefficient; new technologies are being introduced for speeding up applications in production and assembly lines. In this research we address the needs of different technological applications from a conductivity perspective. In the first part of the thesis, the synthesis of soluble conducting polymers in order to make them more processable for potential electronic and photovoltaic applications is presented. Soluble conducting polymers of 3-hexylthiophene, 3-octylthiophene, 3-decylthiophene and 3-dodecylthiophene were synthesized electrochemically and thus, doped during synthesis. It was found that the conductivities; molecular weights and degrees of polymerization of the polymers strongly depend on the side chain's length. The substitution of alkyl side chains decreases the reactivity of the growing chain, and with an increasing side-chain length, all of these properties show a decrease. The hexyl substituent, being the shortest of the four side chains, causes the least distortion in the background, has the highest conjugation, and has the highest shift in the UV spectrum when it polymerizes. As the length of the side chain increases, the shift in the UV spectrum decreases, too. Decrease in the pi-stacking, conjugation and delocalization decreases the conductivity. This gives the material an opportunity to be used in photovoltaic applications. In the second part of the thesis, a conducting adhesive formulation that eliminates the need for heat or other expensive and rather bothersome application methods to activate the adhesive is investigated. Using the quick

  11. Quantum Conductance in Metal Nanowires

    NASA Astrophysics Data System (ADS)

    Ugarte, Daniel

    2004-03-01

    Quantum Conductance in Metal Nanowires D. Ugarte Brazilian National Synchrotron Light Laboratory C.P. 6192, 13084-971 Campinas SP, Brazil. Electrical transport properties of metallic nanowires (NWs) have received great attention due to their quantum conductance behavior. Atomic scale wires can be generated by stretching metal contacts; during the elongation and just before rupture, the NW conductance shows flat plateaus and abrupt jumps of approximately a conductance quantum. In this experiments, both the NW atomic arrangement and conductance change simultaneously, making difficult to discriminate electronic and structural effects. In this work, the atomic structure of NWs was studied by time-resolved in situ experiments in a high resolution transmission electron microscope, while their electrical properties using an UHV mechanically controllable break junction (MCBJ). From the analysis of numerous HRTEM images and videos, we have deduced that metal (Au, Ag, Pt, etc.) junctions generated by tensile deformation are crystalline and free of defects. The neck structure is strongly dependent on the surface properties of the analyzed metal, this was verified by comparing different metal NWs (Au, Ag, Cu), which have similar atomic structure (FCC), but show very different faceting patterns. The correlation between the observed structural and transport properties of NW points out that the quantum conductance behavior is defined by preferred atomic arrangement at the narrowest constriction. In the case of magnetic (ex. Fe,Co,Ni) or quasi-magnetic (ex. Pd) wires, we have observed that one-atom-thick structures show a conductance of half the quantum as expected for a fully spin polarized current. This phenomenon seems to occur spontaneously for magnetic suspended atom-chains in zero magnetic field and at room temperature. These results open new opportunities for spin control in nanostructures. Funded by FAPESP, LNLS and CNPq.

  12. Thermal conductivity of carbonate rocks

    USGS Publications Warehouse

    Thomas, J.; Frost, R.R.; Harvey, R.D.

    1973-01-01

    The thermal conductivities of several well-defined carbonate rocks were determined near 40??C. Values range from 1.2 W m-1 C-1 for a highly porous chalk to 5.1 W m-1 C-1 for a dolomite. The thermal conductivity of magnesite (5.0) is at the high end of the range, and that for Iceland Spar Calcite (3.2) is near the middle. The values for limestones decrease linearly with increasing porosity. Dolomites of comparable porosity have greater thermal conductivities than limestones. Water-sorbed samples have expected greater thermal conductivities than air-saturated (dry) samples of the same rock. An anomalously large increase in the thermal conductivity of a water-sorbed clayey dolomite over that of the same sample when dry is attributed to the clay fraction, which swells during water inhibition, causing more solid-to-solid contacts within the dolomite framework. Measurements were made with a Colora Thermoconductometer. Chemical and mineralogical analyses were made and tabulated. Porosity of the rocks was determined by mercury porosimetry and also from density measurements. The Iceland Spar Calcite and magnesite were included for reference. ?? 1973.

  13. Conformational gating of DNA conductance

    PubMed Central

    Artés, Juan Manuel; Li, Yuanhui; Qi, Jianqing; Anantram, M. P.; Hihath, Joshua

    2015-01-01

    DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. The conductance of the two conformations displays weak length dependencies, as is expected for guanine-rich sequences, and can be fit with a coherence-corrected hopping model. These results are supported by ab initio electronic structure calculations that indicate that the highest occupied molecular orbital is more disperse in the A-form DNA case. These results demonstrate that DNA can behave as a promising molecular switch for molecular electronics applications and also provide additional insights into the huge dispersion of DNA conductance values found in the literature. PMID:26648400

  14. Thermal Conductivity in Supercooled Water

    NASA Astrophysics Data System (ADS)

    Biddle, John; Holten, Vincent; Sengers, Jan; Anisimov, Mikhail

    2013-03-01

    The heat capacity of supercooled water, measured down to -37 C, shows an anomalous increase as temperature decreases. The thermal diffusivity, the ratio of thermal conductivity and the heat capacity per unit volume, shows a decrease. These anomalies may be associated with a hypothetical liquid-liquid critical point in metastable water below the line of homogeneous nucleation. The data suggest that the thermal conductivity does not show a significant critical enhancement, in contrast to what is observed near the vapor-liquid critical point. We have used mode-coupling theory to investigate the possible effect of critical fluctuations on the thermal conductivity of supercooled water, and shown that indeed this effect would be too small to be measurable at experimentally accessible temperatures. We discuss physical reasons for the striking difference between the vapor-liquid and liquid-liquid critical enhancements of thermal conductivity in water. We also discuss the discrepancy between the thermal conductivity calculated from experimental data and that obtained by computer simulations of the TIP5P water-like model. American Chemical Society Petroleum Research Fund Grant No. 52666-ND6

  15. Conformational gating of DNA conductance.

    PubMed

    Artés, Juan Manuel; Li, Yuanhui; Qi, Jianqing; Anantram, M P; Hihath, Joshua

    2015-01-01

    DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. The conductance of the two conformations displays weak length dependencies, as is expected for guanine-rich sequences, and can be fit with a coherence-corrected hopping model. These results are supported by ab initio electronic structure calculations that indicate that the highest occupied molecular orbital is more disperse in the A-form DNA case. These results demonstrate that DNA can behave as a promising molecular switch for molecular electronics applications and also provide additional insights into the huge dispersion of DNA conductance values found in the literature. PMID:26648400

  16. Electrical conductivity of chondritic meteorites

    NASA Technical Reports Server (NTRS)

    Duba, AL; Didwall, E. M.; Burke, G. J.; Sonett, C. P.

    1987-01-01

    The electrical conductivity of samples of the Murchison and Allende carbonaceous chondrites is 4 to 6 orders of magnitude greater than rock forming minerals such as olivine for temperatures up to 700 C. The remarkably high electrical conductivity of these meteorites is attributed to carbon at the grain boundaries. Much of this carbon is produced by pyrolyzation of hydrocarbons at temperatures in excess of 150 C. As the temperature increases, light hydrocarbons are driven off and a carbon-rich residue or char migrates to the grain boundaries enhancing electrical conductivity. Assuming that carbon was present at the grain boundaries in the material which comprised the meteorite parent bodies, the electrical heating of such bodies was calculated as a function of body size and solar distance during a hypothetical T-Tauri phase of the sun. Input conductivity data for the meteorite parent body were the present carbonaceous chondrite values for temperatures up to 840 C and the electrical conductivity values for olivine above 840 C.

  17. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT

    PubMed Central

    Savani, Bipin N.; Labopin, Myriam; Kröger, Nicolaus; Finke, Jürgen; Ehninger, Gerhard; Niederwieser, Dietger; Schwerdtfeger, Rainer; Bunjes, Donald; Glass, Bertram; Socié, Gerard; Ljungman, Per; Craddock, Charles; Baron, Frédéric; Ciceri, Fabio; Gorin, Norbert Claude; Esteve, Jordi; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

    2016-01-01

    The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs

  18. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors.

    PubMed

    Solomon, Scott R; Sizemore, Connie A; Sanacore, Melissa; Zhang, Xu; Brown, Stacey; Holland, H Kent; Morris, Lawrence E; Bashey, Asad

    2015-07-01

    We enrolled 30 patients on a prospective phase II trial utilizing a total body irradiation (TBI)-based myeloablative preparative regimen (fludarabine 30 mg/m2/day × 3 days and TBI 150 cGy twice per day on day -4 to -1 [total dose 1200 cGy]) followed by infusion of unmanipulated peripheral blood stem cells from a haploidentical family donor (haplo). Postgrafting immunosuppression consisted of cyclophosphamide 50 mg/kg/day on days 3 and 4, mycophenolate mofetil through day 35, and tacrolimus through day 180. Median patient age was 46.5 years (range, 24 to 60). Transplantation diagnosis included acute myelogenous leukemia (n = 16), acute lymphoblastic leukemia (n = 6), chronic myelogenous leukemia (n = 5), myelodysplastic syndrome (n = 1), and non-Hodgkin's lymphoma (n = 2). Using the Dana Farber/Center for International Blood and Marrow Transplant Research/Disease Risk Index (DRI), patients were classified as low (n = 4), intermediate (n = 12), high (n = 11), and very high (n = 3) risk. All patients engrafted with a median time to neutrophil and platelet recovery of 16 and 25 days, respectively. All evaluable patients achieved sustained complete donor T cell and myeloid chimerism by day +30. Acute graft-versus-host disease (GVHD) grades II to IV and III and IV was seen in 43% and 23%, respectively. The cumulative incidence of chronic GVHD was 56% (severe in 10%). After a median follow-up of 24 months, the estimated 2-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality, and relapse rate were 78%, 73%, 3%, and 24%, respectively. Two-year DFS and relapse rate in patients with low/intermediate risk disease was 100% and 0%, respectively, compared with 39% and 53% for patients with high/very high risk disease. When compared with a contemporaneously treated cohort of patients at our institution receiving myeloablative HLA-matched unrelated donor (MUD) transplantation (acute myelogenous leukemia [n = 17], acute lymphoblastic leukemia [n = 15

  19. Temperature correction in conductivity measurements

    USGS Publications Warehouse

    Smith, Stanford H.

    1962-01-01

    Electrical conductivity has been widely used in freshwater research but usual methods employed by limnologists for converting measurements to conductance at a given temperature have not given uniformly accurate results. The temperature coefficient used to adjust conductivity of natural waters to a given temperature varies depending on the kinds and concentrations of electrolytes, the temperature at the time of measurement, and the temperature to which measurements are being adjusted. The temperature coefficient was found to differ for various lake and stream waters, and showed seasonal changes. High precision can be obtained only by determining temperature coefficients for each water studied. Mean temperature coefficients are given for various temperature ranges that may be used where less precision is required.

  20. Conductive mechanism in manganite materials

    NASA Astrophysics Data System (ADS)

    Liu, Xianming; Zhu, Hong; Zhang, Yuheng

    2002-01-01

    We describe a model in which f(T)=M(T)/Mmax represents both the fraction of the itinerant electron density in the double-exchange (DE) theory and the magnetization σ in the current carrier density collapse (CCDC) theory. With this model, we have checked the DE and CCDC theories with our experimental results of the transport behavior. The DE theory yields agreement with the experimental resistivity excellently, in which the conductivity is the sum of the polaronic and itinerant electronic conductivity for the insulator-metal transition regime. The fitting curves of the resistivity by the CCDC theory deviate from the experiment seriously. This might be caused by the improper assumption of the temperature-dependent carrier density and the temperature-independent carrier mobility. Therefore, it is concluded that the DE theory is more suitable to explain the conductive mechanism in perovskite manganites.