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1.
BMC Cardiovasc Disord ; 24(1): 158, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486153

RESUMO

BACKGROUND: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. METHODS: We compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors. RESULTS: Our sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm2, 95% CI [18.8 - 20.9]) and men (22.3 mm2, 95% CI [21.4 - 23.2]; White women (20.0 mm2, 95% CI [19.4-20.5]) and men (23.6 mm2, 95% CI [23.0-24.2]); and Black women (21.6 mm2, 95% CI [21.0 - 22.2]) and men (26.0 mm2, 95% CI [25.3 - 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated. CONCLUSIONS: South Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.


Assuntos
Aterosclerose , Vasos Coronários , Feminino , Humanos , Masculino , Povo Asiático , Cálcio , Vasos Coronários/diagnóstico por imagem , Coração , Brancos , Negro ou Afro-Americano
2.
BMC Med ; 18(1): 408, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33334341

RESUMO

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.


Assuntos
Assistência ao Convalescente/estatística & dados numéricos , COVID-19 , Fragilidade/complicações , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/reabilitação , Estudos de Coortes , Comorbidade , Feminino , Fragilidade/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , SARS-CoV-2
3.
Phys Rev Lett ; 120(13): 135005, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29694175

RESUMO

Three-dimensional laser-plasma interaction simulations show that laser frequency detuning by an amount achievable with current laser technology can be used to suppress the two-plasmon decay (TPD) instability and the corresponding hot-electron generation. For the plasma conditions and laser configuration in a direct-drive inertial confinement fusion implosion on the OMEGA laser, the simulations show that ∼0.7% laser frequency detuning is sufficient to eliminate TPD-driven hot-electron generation in current experiments. This allows for higher ablation pressures in future implosion designs by using higher laser intensities.

4.
Phys Rev Lett ; 120(5): 055001, 2018 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-29481170

RESUMO

Planar laser-plasma interaction (LPI) experiments at the National Ignition Facility (NIF) have allowed access for the first time to regimes of electron density scale length (∼500 to 700 µm), electron temperature (∼3 to 5 keV), and laser intensity (6 to 16×10^{14} W/cm^{2}) that are relevant to direct-drive inertial confinement fusion ignition. Unlike in shorter-scale-length plasmas on OMEGA, scattered-light data on the NIF show that the near-quarter-critical LPI physics is dominated by stimulated Raman scattering (SRS) rather than by two-plasmon decay (TPD). This difference in regime is explained based on absolute SRS and TPD threshold considerations. SRS sidescatter tangential to density contours and other SRS mechanisms are observed. The fraction of laser energy converted to hot electrons is ∼0.7% to 2.9%, consistent with observed levels of SRS. The intensity threshold for hot-electron production is assessed, and the use of a Si ablator slightly increases this threshold from ∼4×10^{14} to ∼6×10^{14} W/cm^{2}. These results have significant implications for mitigation of LPI hot-electron preheat in direct-drive ignition designs.

5.
J Fish Biol ; 92(3): 828-845, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29411379

RESUMO

Research on the values of fish populations and fisheries has primarily focused on bio-economic aspects; a more nuanced and multidimensional perspective is mostly neglected. Although a range of social aspects is increasingly being considered in fisheries research, there is still no clear understanding as to how to include these additional values within management policies nor is there a cogent appreciation of the major knowledge gaps that should be tackled by future research. This paper results from a workshop held during the 50th anniversary symposium of the Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017. Here, we aim to highlight the current knowledge gaps on the values of fish populations and fisheries thus directing future research. To this end, we present eight questions that are deeply relevant to understanding the values of fish populations and fisheries. These can be applied to all habitats and fisheries, including freshwater, estuarine and marine.


Assuntos
Conservação dos Recursos Naturais/métodos , Peixes/fisiologia , Animais , Biodiversidade , Ecossistema , Pesqueiros , Bases de Conhecimento , Dinâmica Populacional
6.
Phys Rev Lett ; 113(10): 105001, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25238364

RESUMO

The linear stability of multiple coherent laser beams with respect to two-plasmon-decay instability in an inhomogeneous plasma in three dimensions has been determined. Cooperation between beams leads to absolute instability of long-wavelength decays, while shorter-wavelength shared waves are shown to saturate convectively. The multibeam, in its absolutely unstable form, has the lowest threshold for most cases considered. Nonlinear calculations using a three-dimensional extended Zakharov model show that Langmuir turbulence created by the absolute instability modifies the convective saturation of the shorter-wavelength modes, which are seen to dominate at late times.

7.
Phys Rev Lett ; 112(14): 145001, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24765976

RESUMO

Half-harmonic emission spectra and images taken during directly driven implosions show that the two-plasmon decay (TPD) instability is driven nonuniformly over the target surface and that multibeam effects dominate this instability. The images show a spatially limited extent of the TPD instability. A prominent spectral feature is used to determine the electron temperature in the corona. Near threshold the temperatures agree with one-dimensional hydrodynamic predictions but exceed them by ∼10% above the TPD threshold. Two-dimensional hydrodynamic simulations indicate that a significant part (∼20%) of the laser intensity must be locally absorbed by the TPD instability (i.e., by collisional damping of the electron plasma waves) to maintain these temperature islands.

8.
Afr J Med Med Sci ; 43(Suppl 1): 5-13, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29578211

RESUMO

BACKGROUND: Female Sex Workers (FSWs) are key reservoirs of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) from which transmission to the general population fuels epidemics. STIs amplify HIV infectiousness and susceptibility. We determined the status of HIV and STIs among brothel-based FSWs in Jos as part of an ongoing prevention intervention. METHOD: Between January and May 2012, consenting consecutive brothel-based FSWs were recruited from previously designated brothels across Jos. HIV counseling and testing as well as screening for gonorrhoea, syphilis, trichomonasis, candidasis and Bacteria vaginosis (BV) were performed. Positive cases were provided free treatment and follow-up at Solat Women Hospital, Jos. Ethical clearance was obtained from Jos University Teaching Hospital (JUTH) ethical committee. RESULT: Two hundred FSWs aged 27.6 ± 4.6 years (range 15-55 years) were recruited and of these, 47 (23.5%) were HIV Positive, 20 (10.0%) had syphilis, 9 (4.5%) had Neisseria gonorrhea, 3 (1.5%) had Trichomonas vaginalis and 86 (43.0%) had BV. The association between HIV and bacterial vaginosis was statistically significant (OR of 2.2, 95% CI of 1.1-4.2, P-value=0.02). In comparison to similar prevalence in 2006, the current findings represent 51.5% decline in HIV prevalence, 40.8% decline for syphilis and over 83.3% decline in prevalence for Trichomonas vaginalis. There was no significant change in the prevalence of Neisseria gonorrhoea and BV. CONCLUSION: The prevalence of HIV and STIs among brothel-based FSWs in Jos remain unacceptably high, although, there is a declining trend. A comprehensive HIV prevention program targeting these women is required to block transmission to the general population.

9.
Dev Cogn Neurosci ; 68: 101402, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917647

RESUMO

In electroencephalographic (EEG) data, power-frequency slope exponents (1/f_ß) can provide non-invasive markers of in vivo neural activity excitation-inhibition (E:I) balance. E:I balance may be altered in neurodevelopmental conditions; hence, understanding how 1/fß evolves across infancy/childhood has implications for developing early assessments/interventions. This systematic review (PROSPERO-ID: CRD42023363294) explored the early maturation (0-26 yrs) of resting-state EEG 1/f measures (aperiodic [AE], power law [PLE] and Hurst [HE] exponents), including studies containing ≥1 1/f measures and ≥10 typically developing participants. Five databases (including Embase and Scopus) were searched during March 2023. Forty-two studies were identified (Nparticipants=3478). Risk of bias was assessed using the Quality Assessment with Diverse Studies tool. Narrative synthesis of HE data suggests non-stationary EEG activity occurs throughout development. Age-related trends were complex, with rapid decreases in AEs during infancy and heterogenous changes thereafter. Regionally, AE maxima shifted developmentally, potentially reflecting spatial trends in maturing brain connectivity. This work highlights the importance of further characterising the development of 1/f measures to better understand how E:I balance shapes brain and cognitive development.


Assuntos
Encéfalo , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Lactente , Criança , Pré-Escolar , Adolescente , Recém-Nascido , Adulto Jovem , Desenvolvimento Infantil/fisiologia , Adulto , Ondas Encefálicas/fisiologia
10.
Rapid Commun Mass Spectrom ; 27(5): 635-42, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23413223

RESUMO

RATIONALE: In situ analytical techniques that require the storage and delivery of reagents (e.g., acidic or basic solutions) have inherent durability limitations. The reagentless electrolytic technique for pH modification presented here was developed primarily to ease and to extend the longevity of dissolved inorganic carbon (DIC) determinations in seawater, but can also be used for other analytical methods. DIC, a primary carbon dioxide (CO(2)) system variable along with alkalinity, controls seawater pH, carbonate saturation state, and CO(2) fugacity. Determinations of these parameters are central to an understanding of ocean acidification and global climate change. METHODS: Electrodes fabricated with electroactive materials, including manganese(III) oxide (Mn(2)O(3)) and palladium (Pd), were examined for potential use in electrolytic acidification. In-line acidification techniques were evaluated using a bench-top membrane introduction mass spectrometry (MIMS) setup to determine the DIC content of artificial seawater. Linear least-squares (LLSQ) calibrations for DIC concentration determinations over a range between 1650 and 2400 µmol kg(-1) were obtained, using both the novel electrolytic and conventional acid addition techniques. RESULTS: At sample rates of 4.5 mL min(-1), electrodes clad with Mn(2)O(3) and Pd were able to change seawater pH from 7.6 to 2.8 with a power consumption of less than 3 W. Although calibration curves were influenced by sampling rates at a flow of 4.5 mL min(-1), the 1σ measurement precision for DIC was of the order of ±20 µmol kg(-1). CONCLUSIONS: Calibrations obtained with the novel reagentless technique and the in-line addition of strong acid showed similar capabilities for DIC quantification. However, calculations of power savings for the reagentless technique relative to the mechanical delivery of stored acid demonstrated substantial advantages of the electrolytic technique for long-term deployments (>1 year).


Assuntos
Compostos Inorgânicos de Carbono/análise , Carbono/análise , Espectrometria de Massas/métodos , Água do Mar/química , Calibragem , Eletrodos , Eletrólise/métodos , Concentração de Íons de Hidrogênio , Modelos Lineares , Compostos de Manganês/química , Óxidos/química , Paládio/química , Reprodutibilidade dos Testes
11.
Front Bioeng Biotechnol ; 11: 1213021, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675407

RESUMO

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

12.
Phys Rev Lett ; 108(16): 165003, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22680726

RESUMO

Measurements of the hot-electron generation by the two-plasmon-decay instability are made in plasmas relevant to direct-drive inertial confinement fusion. Density-scale lengths of 400 µm at n(cr)/4 in planar CH targets allowed the two-plasmon-decay instability to be driven to saturation for vacuum intensities above ~3.5×10(14) W cm(-2). In the saturated regime, ~1% of the laser energy is converted to hot electrons. The hot-electron temperature is measured to increase rapidly from 25 to 90 keV as the laser beam intensity is increased from 2 to 7×10(14) W cm(-2). This increase in the hot-electron temperature is compared with predictions from nonlinear Zakharov models.

13.
Phys Rev Lett ; 109(15): 155007, 2012 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-23102322

RESUMO

The energy in hot electrons produced by the two plasmon decay instability, in planar targets, is measured to be the same when driven by one or two laser beams and significantly reduced with four for a constant overlapped intensity on the OMEGA EP. This is caused by multiple beams sharing the same common electron-plasma wave. A model, consistent with the experimental results, predicts that multiple laser beams can only drive a resonant common two plasmon decay electron-plasma wave in the region of wave numbers bisecting the beams. In this region, the gain is proportional to the overlapped laser beam intensity.

14.
Gynecol Oncol Rep ; 42: 101038, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35832044

RESUMO

•Yolk sac tumors are quite rare in post-menopausal women.•Yolk sac tumors with endometrial primary origin also may present with abnormal uterine bleeding.•Patients with unclear abdominal symptoms, mass on imaging, and positive tumor markers raises suspicion of yolk sac tumor.

15.
Environ Int ; 158: 106903, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601394

RESUMO

In this review of reviews, we overview the current global body of available evidence from structured reviews of epidemiological studies that explore human health outcomes associated with exposure to phthalates (chemical plasticisers commonly found in plastics). We found robust evidence for an association with lower semen quality, neurodevelopment and risk of childhood asthma, and moderate to robust evidence for impact on anogenital distance in boys. We identified moderate evidence for an association between phthalates/metabolites and low birthweight, endometriosis, decreased testosterone, ADHD, Type 2 diabetes and breast/uterine cancer. There was some evidence for other outcomes including anofourchette distance, fetal sex hormones, pre-term birth, lower antral follicle count, reduced oestrodiol, autism, obesity, thyroid function and hearing disorders. We found no reviews of epidemiological human studies on the impact of phthalates from recycled plastics on human health. We recommend that future research should use urine samples as exposure measures, consider confounders in analyses and measure impacts on female reproductive systems. Our findings align with emerging research indicating that health risks can occur at exposure levels below the "safe dose" levels set out by regulators, and are of particular concern given potential additive or synergistic "cocktail effects" of chemicals. This raises important policy and regulatory issues for identifying and controlling plastics and health related impacts and highlights a need for more research into substances of concern entering plastics waste streams via recycling.


Assuntos
Diabetes Mellitus Tipo 2 , Ácidos Ftálicos , Exposição Ambiental , Feminino , Humanos , Masculino , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade , Análise do Sêmen
16.
J Hosp Infect ; 106(2): 376-384, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32702463

RESUMO

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/transmissão , Infecção Hospitalar/mortalidade , Infecção Hospitalar/transmissão , Idoso Fragilizado/estatística & dados numéricos , Mortalidade Hospitalar , Pneumonia Viral/mortalidade , Pneumonia Viral/transmissão , Medição de Risco/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Infecção Hospitalar/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
17.
Phys Rev E Stat Nonlin Soft Matter Phys ; 79(6 Pt 2): 066409, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19658614

RESUMO

Expressions for the yield of electron-positron pairs, their energy spectra, and production rates have been obtained in the interaction of multi-kJ pulses of high-intensity laser light interacting with solid targets. The Bethe-Heitler conversion of hard x-ray bremsstrahlung [D. A. Gryaznykh, Y. Z. Kandiev, and V. A. Lykov, JETP Lett. 67, 257 (1998); K. Nakashima and H. Takabe, Phys. Plasmas 9, 1505 (2002)] is shown to dominate over direct production (trident process) [E. P. Liang, S. C. Wilks, and M. Tabak, Phys. Rev. Lett. 81, 4887 (1998)]. The yields and production rates have been optimized as a function of incident laser intensity by the choice of target material and dimensions, indicating that up to 5 x 10 (11) pairs can be produced on the OMEGA EP laser system [L. J. Waxer, Opt. Photonics News 16, 30 (2005)]. The corresponding production rates are high enough to make possible the creation of a pair plasma.

18.
Phys Rev E ; 99(3-1): 033203, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30999431

RESUMO

Raman side scatter, whereby scattered light is resonant while propagating perpendicularly to a density gradient in a plasma, was identified experimentally in planar-target experiments at the National Ignition Facility at intensities orders of magnitudes below the threshold for absolute instability. We have derived a new theoretical description of convective Raman side scatter below the absolute threshold, validated by numerical simulations. We show that inertial confinement fusion experiments at full ignition scale, i.e., with mm-scale spot sizes and density scale lengths, are prone to increased coupling losses from Raman side scatter as the instability can extend from the absolute regime near the quarter-critical density to the convective regime at lower electron densities.

19.
Cell Death Differ ; 14(1): 128-36, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16645638

RESUMO

All BH3-only proteins, key initiators of programmed cell death, interact tightly with multiple binding partners and have sequences of low complexity, properties that are the hallmark of intrinsically unstructured proteins (IUPs). We show, using spectroscopic methods, that the BH3-only proteins Bim, Bad and Bmf are unstructured in the absence of binding partners. Detailed sequence analyses are consistent with this observation and suggest that most BH3-only proteins are unstructured. When Bim binds and inactivates prosurvival proteins, most residues remain disordered, only the BH3 element becomes structured, and the short alpha-helical molecular recognition element can be considered to behave as a 'bead on a string'. Coupled folding and binding is typical of many IUPs that have important signaling roles, such as BH3-only proteins, as the inherent structural plasticity favors interaction with multiple targets. This understanding offers promise for the development of BH3 mimetics, as multiple modes of binding are tolerated.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Reguladoras de Apoptose/química , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Membrana/química , Proteínas Proto-Oncogênicas/química , Proteína de Morte Celular Associada a bcl/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/isolamento & purificação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/isolamento & purificação , Proteína 11 Semelhante a Bcl-2 , Dicroísmo Circular , Proteínas de Membrana/genética , Proteínas de Membrana/isolamento & purificação , Proteínas de Membrana/metabolismo , Camundongos , Ressonância Magnética Nuclear Biomolecular , Dobramento de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/isolamento & purificação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/isolamento & purificação , Proteína de Morte Celular Associada a bcl/metabolismo
20.
Ultrasound Med Biol ; 32(4): 579-85, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16616603

RESUMO

Predicting the acoustic response of an encapsulated microbubble to ultrasound requires an accurate assessment of the mechanical properties of the microbubble shell. Atomic force microscopy (AFM) provides an unprecedented spatial and force resolution of the order of Angstroms and subnanonewtons, respectively. It is introduced here as a means to interrogate microbubbles manufactured for ultrasonic imaging. The advantage of AFM over scanning electron microscopy (SEM) is that the microbubbles need not be subjected to a low temperature or low-pressure environment. The microbubbles were interrogated in a liquid environment, which could potentially be a simulated physiological environment. AFM was used in tapping mode imaging to reveal topographical detail of biSphere microbubbles. Because microbubbles are large objects compared with the overall size of usual AFM tips, a convolution between the AFM tip and the microbubble was typical of the acquired topographies. However, a part of the top half of the bubble was imaged with nanometer resolution, and roughness measurements are reported. Force-distance curves were captured using contact mode AFM. The range of stiffness or effective spring constant of biSphere was found to be between 1 and 6 N m(-1). In conclusion, the AFM is proposed here for the first time as a tool to image the surface of bubbles at the nanometer range in liquid and to perform reproducible measurements on the mechanical properties of individual microbubbles.


Assuntos
Meios de Contraste , Microbolhas , Ultrassonografia/métodos , Fenômenos Biomecânicos , Elasticidade , Humanos , Imageamento Tridimensional , Microscopia de Força Atômica/métodos , Nanotecnologia , Estresse Mecânico , Propriedades de Superfície
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