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1.
Phys Rev Lett ; 132(6): 065102, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394591

RESUMO

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

2.
Phys Rev Lett ; 129(7): 075001, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36018710

RESUMO

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

3.
Tech Coloproctol ; 25(6): 721-726, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33881657

RESUMO

BACKGROUND: The technical difficulty and steep learning curve of transanal total mesorectal excision (taTME) has limited widespread adoption. The single-port (SP) daVinci robot is designed to facilitate single-incision and natural-orifice transluminal endoscopic surgery (NOTES). This paper describes the first clinical experience of single-port robotic taTME (SP rTaTME). METHODS: This was a prospective study on consecutive patients with rectal cancer who underwent SP rTaTME proctosigmoidectomy with handsewn coloanal anastomosis in December 2018 and January 2019. The primary outcome was technical feasibility of the procedure. The secondary outcomes include blood loss, intraoperative complications, length of hospital stay, quality of the TME specimen, short- and long-term morbidity and mortality, as well as short-term oncologic follow -up. RESULTS: There were two patients, a 48-year-old male and a 38-year-old female. Both operations were completed successfully without complications or conversion. Estimated blood loss was 200 mL and 130 mL. In both cases the TME was completed transanally using the SP robot. In the first patient, the abdominal portion was completed through an abdominal single-incision; in the second patient the operation was entirely performed transanally as a pure NOTES procedure. In both cases, the final pathology report showed a complete TME with negative margins. Patients were discharged on postoperative day 3 and 4,respectively. There was no long-term morbidity or mortality. CONCLUSIONS: SP rTaTME is feasible and can be safely performed. It provides excellent optics and dexterity to work in a limited space. Future studies are required to further define the safety profile and the ultimate utility of the SP robot for taTME.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgia Endoscópica Transanal , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Neoplasias Retais/cirurgia , Reto/cirurgia
4.
Br Poult Sci ; 62(5): 701-709, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33970711

RESUMO

1. The following study provides the first data on the detection and types of Listeria monocytogenes isolated from broiler chickens during processing and from six Taiwanese abattoir environments.2. Listeria monocytogenes was not detected in any cloacal (n = 120) or environmental (n = 256) samples collected before and during processing, indicating that faecal material and the environment of abattoirs were not important sources of L. monocytogenes for poultry carcases. However, 28 of 246 (11.4%; 95% CI: 7.7-16.0) rinse samples collected from carcases post-evisceration from three abattoirs were positive for L. monocytogenes.3. The only serotypes detected were 1/2a (82.1%; 95% CI: 63.1-93.9) and 1/2b (14.3%; 95% CI: 4.0-32.7), with 3.6% (95% CI: 0.1-18.3) non-typable isolates.4. Characterisation by Pulsed Field Gel Electrophoresis (PFGE) identified five PFGE types, confirming cross-contamination with L. monocytogenes during evisceration, chilling and post-chilling.5. These findings highlight the potential for cross-contamination to occur through direct contact between carcases, especially whilst in chilling tanks.


Assuntos
Listeria monocytogenes , Matadouros , Animais , Galinhas , Eletroforese em Gel de Campo Pulsado/veterinária , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Taiwan
5.
Am J Transplant ; 15(6): 1615-22, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25809272

RESUMO

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.


Assuntos
Apolipoproteínas/genética , Negro ou Afro-Americano/genética , Variação Genética/genética , Rejeição de Enxerto/genética , Nefropatias/cirurgia , Transplante de Rim , Lipoproteínas HDL/genética , Doadores de Tecidos , Adolescente , Adulto , Alabama , Aloenxertos , Apolipoproteína L1 , Feminino , Genótipo , Rejeição de Enxerto/etnologia , Rejeição de Enxerto/mortalidade , Humanos , Nefropatias/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , North Carolina , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
6.
Psychol Med ; 45(11): 2333-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25727375

RESUMO

BACKGROUND: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. METHOD: One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). RESULTS: Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = -0.28, p = 0.007). CONCLUSIONS: Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.


Assuntos
Cognição , Depressão/psicologia , Função Executiva , Tempo de Reação , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Testes Neuropsicológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Adulto Jovem
7.
Mol Psychiatry ; 19(12): 1267-74, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24296977

RESUMO

A study of genome-wide gene expression in major depressive disorder (MDD) was undertaken in a large population-based sample to determine whether altered expression levels of genes and pathways could provide insights into biological mechanisms that are relevant to this disorder. Gene expression studies have the potential to detect changes that may be because of differences in common or rare genomic sequence variation, environmental factors or their interaction. We recruited a European ancestry sample of 463 individuals with recurrent MDD and 459 controls, obtained self-report and semi-structured interview data about psychiatric and medical history and other environmental variables, sequenced RNA from whole blood and genotyped a genome-wide panel of common single-nucleotide polymorphisms. We used analytical methods to identify MDD-related genes and pathways using all of these sources of information. In analyses of association between MDD and expression levels of 13 857 single autosomal genes, accounting for multiple technical, physiological and environmental covariates, a significant excess of low P-values was observed, but there was no significant single-gene association after genome-wide correction. Pathway-based analyses of expression data detected significant association of MDD with increased expression of genes in the interferon α/ß signaling pathway. This finding could not be explained by potentially confounding diseases and medications (including antidepressants) or by computationally estimated proportions of white blood cell types. Although cause-effect relationships cannot be determined from these data, the results support the hypothesis that altered immune signaling has a role in the pathogenesis, manifestation, and/or the persistence and progression of MDD.


Assuntos
Transtorno Depressivo Maior/genética , Interferon Tipo I/genética , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Autorrelato , Análise de Sequência de RNA/métodos , Transdução de Sinais/genética , População Branca/genética , Adulto Jovem
8.
Invest New Drugs ; 32(3): 526-34, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24464266

RESUMO

INTRODUCTION: Vorinostat is a small molecule inhibitor of class I and II histone deacetylases with preclinical activity in melanoma. METHODS: We evaluated 32 patients with advanced primary cutaneous or ocular melanoma in a multi-institutional setting (PMH Phase II Consortium) with continuous daily oral vorinostat 400 mg. The primary endpoint was response rate by RECIST, with time to progression as a secondary endpoint. The study was designed to distinguish a response rate of 20 % from a RR of 5 % and to distinguish a 2 month median progression-free survival (PFS), from one of 3.1 months. The study proceeded to stage 2 following 2 of 16 responses.. We also assessed VEGF, FGF levels, P52 polymorphisms and chromatin-associated proteins as potential biomarkers. RESULTS: Therapy was associated with significant side effects, including fatigue, nausea, lymphopenia, and hyperglycemia. Eleven patients experienced at least one grade 3 or higher adverse event. There were two confirmed PRs in patients with cutaneous melanoma. Sixteen patients had stable disease and 14 patients had progressive disease for best response. In addition, two patients with cutaneous melanoma scored as stable disease had early unconfirmed partial responses with subsequent progression. Patients with stable disease or partial response (n = 18) had a median progression free survival of 5 months. (range 2-12 months). CONCLUSIONS: Vorinostat demonstrated some early responses and a high proportion of patients with stable disease, but did not meet its primary endpoint of response. Different schedules of this agent with BRAF mutation status and markers of histone acetylation could be explored in melanoma.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Ácidos Hidroxâmicos/farmacologia , Masculino , Melanoma/genética , Melanoma/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias Cutâneas , Proteína Supressora de Tumor p53/genética , Fator A de Crescimento do Endotélio Vascular/sangue , Vorinostat , Melanoma Maligno Cutâneo
9.
Parasite Immunol ; 36(10): 531-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25039932

RESUMO

The M2 subset of macrophages has a critical role to play in host tissue repair, tissue fibrosis and modulation of adaptive immunity during helminth infection. Infection with the helminth, Fasciola hepatica, is associated with M2 macrophages in its mammalian host, and this response is mimicked by its excretory-secretory products (FhES). The tegumental coat of F. hepatica (FhTeg) is another major source of immune-modulatory molecules; we have previously shown that FhTeg can modulate the activity of both dendritic cells and mast cells inhibiting their ability to prime a Th1 immune response. Here, we report that FhTeg does not induce Th2 immune responses but can induce M2-like phenotype in vivo that modulates cytokine production from CD4(+) cells in response to anti-CD3 stimulation. FhTeg induces a RELMα expressing macrophage population in vitro, while in vivo, the expression of Arg1 and Ym-1/2 but not RELMα in FhTeg-stimulated macrophages was STAT6 dependent. To support this finding, FhTeg induces RELMα expression in vivo prior to the induction of IL-13. FhTeg can induce IL-13-producing peritoneal macrophages following intraperitoneal injection This study highlights the important role of FhTeg as an immune-modulatory source during F. hepatica infection and sheds further light on helminth-macrophage interactions.


Assuntos
Antígenos de Helmintos/imunologia , Fasciola hepatica/fisiologia , Fasciolíase/imunologia , Macrófagos/imunologia , Animais , Células Dendríticas/imunologia , Fasciolíase/parasitologia , Interleucina-13/imunologia , Macrófagos Peritoneais/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT6/metabolismo
10.
Biol Cybern ; 108(4): 405-22, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24862556

RESUMO

Activity-dependent synaptic plasticity should be extremely connection specific, though experiments have shown it is not, and biophysics suggests it cannot be. Extreme specificity (near-zero "crosstalk") might be essential for unsupervised learning from higher-order correlations, especially when a neuron has many inputs. It is well known that a normalized nonlinear Hebbian rule can learn "unmixing" weights from inputs generated by linearly combining independently fluctuating nonGaussian sources using an orthogonal mixing matrix. We previously reported that even if the matrix is only approximately orthogonal, a nonlinear-specific Hebbian rule can usually learn almost correct unmixing weights (Cox and Adams in Front Comput Neurosci 3: doi: 10.3389/neuro.10.011.2009 2009). We also reported simulations that showed that as crosstalk increases from zero, the learned weight vector first moves slightly away from the crosstalk-free direction and then, at a sharp threshold level of inspecificity, jumps to a completely incorrect direction. Here, we report further numerical experiments that show that above this threshold, residual learning is driven instead almost entirely by second-order input correlations, as occurs using purely Gaussian sources or a linear rule, and any amount of crosstalk. Thus, in this "ICA" model learning from higher-order correlations, required for unmixing, requires high specificity. We compare our results with a recent mathematical analysis of the effect of crosstalk for exactly orthogonal mixing, which revealed that a second, even lower, threshold, exists below which successful learning is impossible unless weights happen to start close to the correct direction. Our simulations show that this also holds when the mixing is not exactly orthogonal. These results suggest that if the brain uses simple Hebbian learning, it must operate with extraordinarily accurate synaptic plasticity to ensure powerful high-dimensional learning. Synaptic crowding would preclude this when inputs are numerous, and we propose that the neocortex might be distinguished by special circuitry that promotes extreme specificity for high-dimensional nonlinear learning.


Assuntos
Aprendizagem/fisiologia , Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia , Animais , Simulação por Computador , Cibernética , Humanos
11.
Acta Crystallogr D Biol Crystallogr ; 69(Pt 4): 625-34, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23519671

RESUMO

A fast and robust method for determining the parameters for a flat (mask-based) bulk-solvent model and overall scaling in macromolecular crystallographic structure refinement and other related calculations is described. This method uses analytical expressions for the determination of optimal values for various scale factors. The new approach was tested using nearly all entries in the PDB for which experimental structure factors are available. In general, the resulting R factors are improved compared with previously implemented approaches. In addition, the new procedure is two orders of magnitude faster, which has a significant impact on the overall runtime of refinement and other applications. An alternative function is also proposed for scaling the bulk-solvent model and it is shown that it outperforms the conventional exponential function. Similarly, alternative methods are presented for anisotropic scaling and their performance is analyzed. All methods are implemented in the Computational Crystallography Toolbox (cctbx) and are used in PHENIX programs.


Assuntos
Bioengenharia/métodos , Biologia Computacional/métodos , Substâncias Macromoleculares/química , Modelos Moleculares , Algoritmos , Anisotropia , Bioengenharia/tendências , Biologia Computacional/tendências , Cristalografia por Raios X , Substâncias Macromoleculares/metabolismo , Distribuição Normal , Solventes , Fatores de Tempo , Difração de Raios X/métodos , Difração de Raios X/tendências
12.
Phys Rev Lett ; 111(2): 027207, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23889439

RESUMO

We demonstrate that the proximity-induced exchange field H(ex) in ferromagnetic-paramagnetic bilayers can be modulated with an electric field. An electrostatic gate arrangement is used to tune the magnitude of H(ex) in the Al component of EuS/Al bilayers. In samples with H(ex)~2 T, we were able to produce modulations of ±10 mT with the application of perpendicular electric fields of the order of ±10(6) V/cm. We discuss several possible mechanisms accounting for the electric field's influence on the interfacial coupling between the Al layer and the ferromagnetic insulator EuS, along with the prospects of producing a superconducting field-effect transistor.

13.
Parasite Immunol ; 35(7-8): 234-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23495757

RESUMO

Fasciola hepatica tegumental coat antigen (FhTeg) suppresses dendritic cell maturation and function by inhibiting IL-6, tumour necrosis factor (TNF)-α, IL-10 and IL-12 production and CD80, CD86 and CD40 cell surface marker expression in TLR4-stimulated dendritic cells. Fasciola hepatica also impairs dendritic cell function by inhibiting its phagocytic capacity and its ability to prime T cells. We have shown previously that activation of mast cells with bacterial ligands is also inhibited by FhTeg. Fasciola hepatica suppresses LPS-induced NF-κB and MAPK pathway (ERK) activation in these cells. Previously, we demonstrated that FhTeg induces expression of suppressor of cytokine signalling (SOCS)3, a negative regulator of the TLR pathway in mast cells. In this study, we show the same inhibitory effect of FhTeg on the activation of the other members of the MAPKs pathway (ERK, p38, JNK) in dendritic cells and demonstrate an enhanced expression of SOCS3, but not SOCS1, SOCS5 or PIAS3 in this process. These studies enhance our understanding of the immunomodulatory effect of helminth molecules on the TLR pathway.


Assuntos
Antígenos de Helmintos/imunologia , Células Dendríticas/enzimologia , Fasciola hepatica/imunologia , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Animais , Células Dendríticas/imunologia , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Transcrição Gênica , Regulação para Cima
14.
J Vet Pharmacol Ther ; 36(5): 502-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22882087

RESUMO

Plasma disposition of florfenicol in channel catfish was investigated after an oral multidose (10 mg/kg for 10 days) administration in freshwater at water temperatures ranging from 24.7 to 25.9 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After the administration of florfenicol, the mean terminal half-life (t(1/2)), maximum concentration at steady-state (Css (max)), time of Css (max) (T(max)), minimal concentration at steady-state (Css (min)), and Vc /F were 9.0 h, 9.72 µg/mL, 8 h, 2.53 µg/mL, and 0.653 L/kg, respectively. These results suggest that florfenicol administered orally at 10 mg/kg body weight for 10 days could be expected to control catfish bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of <2.5 µg/mL.


Assuntos
Antibacterianos/farmacocinética , Ictaluridae/metabolismo , Tianfenicol/análogos & derivados , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/veterinária , Ictaluridae/sangue , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/veterinária , Tianfenicol/administração & dosagem , Tianfenicol/sangue , Tianfenicol/farmacocinética
15.
Rev Gastroenterol Mex ; 78(3): 151-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23948097

RESUMO

BACKGROUND: The Bristol Stool Form Scale (BSFS) and a modified child-friendly version (M-BSFS) are frequently used in clinical practice and research. These scales have not been validated in children. 3-D stool scale models may be better adapted to the child's development. AIMS: To assess the usefulness of the BSFS, M-BSFS, and a newly developed 3-D stool scale in children. METHODS: Fifty children were asked to rank the picture cards of the BSFS and 3-D models from hardest to softest and to match the pictures with descriptors for each stool type. RESULTS: Thirty percent of the children appropriately characterized the stools as hard, loose, or normal using the BSFS vs. 36.6% with the 3-D model (p=0.27). Appropriate correlation of stools as hard, loose, or normal consistency using the BSFS vs. the 3-D model by age group was: 6 to 11-year-olds, 27.5% vs. 33.3% (p=0.58) and 12 to 17-year-olds, 32.1% vs. 39.5% (p=0.41). Thirty-three percent correlated the BSFS pictures with the correct BSFS words, 46% appropriately correlated with the M-BSFS words, and 46% correlated the 3-D stool models with the correct wording. CONCLUSIONS: The BSFS and M-BSFS that are widely used as stool assessment instruments are not user-friendly for children. The 3-D model was not found to be better than the BSFS and the M-BSFS.


Assuntos
Fezes , Pediatria/normas , Criança , Desenvolvimento Infantil , Constipação Intestinal/diagnóstico , Feminino , Humanos , Imageamento Tridimensional , Masculino , Modelos Biológicos , Projetos Piloto , Inquéritos e Questionários
16.
Acta Crystallogr D Struct Biol ; 79(Pt 7): 666-667, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37338421

RESUMO

Equations in Sections 2.3 and 2.4 of the article by Afonine et al. [Acta Cryst. (2013). D69, 625-634] are corrected.

17.
Phys Rev Lett ; 109(14): 147207, 2012 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-23083279

RESUMO

We present a study of the proximity effect between a ferromagnet and a paramagnetic metal of varying disorder. Thin beryllium films are deposited onto a 5 nm thick layer of the ferromagnetic insulator EuS. This bilayer arrangement induces an exchange field, H(ex), of a few tesla in low-resistance Be films with sheet resistance R≪R(Q), where R(Q)=h/e2 is the quantum resistance. We show that H(ex) survives in very high-resistance films and, in fact, appears to be relatively insensitive to the Be disorder. We exploit this fact to produce a giant low-field magnetoresistance in the correlated-insulator phase of Be films with R≫R(Q).

18.
Mol Psychiatry ; 16(2): 193-201, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20125088

RESUMO

A genome-wide association study was carried out in 1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD. Subjects were genotyped with the Affymetrix 6.0 platform. After extensive quality control procedures, 671 424 autosomal single nucleotide polymorphisms (SNPs) and 25 068 X chromosome SNPs with minor allele frequency greater than 1% were available for analysis. An additional 1 892 186 HapMap II SNPs were analyzed based on imputed genotypic data. Single-SNP logistic regression trend tests were computed, with correction for ancestry-informative principal component scores. No genome-wide significant evidence for association was observed, assuming that nominal P<5 × 10(-8) approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P=1.83 × 10(-7)) in a region that has produced some evidence for linkage to bipolar-I or -II disorder in several studies, within an mRNA detected in human brain tissue (BC053410) and approximately 75 kb upstream of DSEL. Comparing these results with those of a meta-analysis of three MDD GWAS data sets reported in a companion article, we note that among the strongest signals observed in the GenRED sample, the meta-analysis provided the greatest support (although not at a genome-wide significant level) for association of MDD to SNPs within SP4, a brain-specific transcription factor. Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs.


Assuntos
Transtorno Depressivo Maior/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Mapeamento Cromossômico , Europa (Continente) , Feminino , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva , Fatores Sexuais , Fator de Transcrição Sp4/genética
19.
Clin Transplant ; 26(4): E402-11, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22882695

RESUMO

BACKGROUND: Acute allograft rejection after HLA desensitization is common early post-transplant but the sequence of histopathologic changes leading to graft dysfunction has not been well defined. METHODS: We evaluated the early pathogenesis and sequence of antibody-mediated graft damage of 35 desensitized living donor kidney recipients by studying the course of biopsies taken in the very early post-transplant period (<1 month). RESULTS: A total of 14 of the 35 patients met criteria for acute antibody-mediated rejection (AMR). In these patients, the chronologic sequence of pathologic changes was C4d peritubular capillary deposition, acute tubular injury, and peritubular capillaritis, followed by glomerulitis and interstitial inflammation. Classic AMR lesions occurred early, followed by mononuclear cellular infiltration, which comprised CD4 and CD8 T cells and monocytes. Development of graft dysfunction in most patients occurred concurrently with the emergence of graft cellular infiltration, rather than at the earlier time of antibody deposition as detected via C4d deposition. CONCLUSION: These data provide novel insight into the sequence of pathologic changes in patients with AMR post-transplant after HLA desensitization.


Assuntos
Dessensibilização Imunológica , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Transplante de Rim/imunologia , Transplante de Rim/patologia , Citometria de Fluxo , Seguimentos , Humanos , Isoanticorpos/sangue , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
20.
J Vet Pharmacol Ther ; 35(5): 503-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21929526

RESUMO

Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10 mg/kg) of intravenous (i.v.) or oral administration in freshwater at a mean water temperature of 25.4 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After i.v. florfenicol injection, the terminal half-life (t(1/2)), volume of distribution at steady state (V(ss)), and central volume of distribution (V(c)) were 8.25 h, 0.9 and 0.381 L/kg, respectively. After oral administration of florfenicol, the terminal t(1/2), C(max), T(max), and oral bioavailability (F) were 9.11 h, 7.6 µg/mL, 9.2 h, and 1.09, respectively. There was a lag absorption time of 1.67 h in oral dosing. Results from these studies support that 10 mg florfenicol/kg body weight in channel catfish is an efficacious dosage following oral administration.


Assuntos
Antibacterianos/farmacocinética , Ictaluridae/sangue , Tianfenicol/análogos & derivados , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida , Meia-Vida , Injeções Intravenosas , Espectrometria de Massas em Tandem , Tianfenicol/administração & dosagem , Tianfenicol/sangue , Tianfenicol/farmacocinética
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