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Three-dimensional (3D) electronic band structure is fundamental for understanding a vast diversity of physical phenomena in solid-state systems, including topological phases, interlayer interactions in van der Waals materials, dimensionality-driven phase transitions, etc. Interpretation of ARPES data in terms of 3D electron dispersions is commonly based on the free-electron approximation for the photoemission final states. Our soft-X-ray ARPES data on Ag metal reveals, however, that even at high excitation energies the final states can be a way more complex, incorporating several Bloch waves with different out-of-plane momenta. Such multiband final states manifest themselves as a complex structure and added broadening of the spectral peaks from 3D electron states. We analyse the origins of this phenomenon, and trace it to other materials such as Si and GaN. Our findings are essential for accurate determination of the 3D band structure over a wide range of materials and excitation energies in the ARPES experiment.
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Spectral luminescence, kinetic and energetic properties of hexachlorosubphthalocyaninatoboron(III) chloride and its azaanalogue containing fused pyrazine fragments instead of benzene rings were studied at 298 and 77 K. Weak phosphorescence of complexes was detected and characterized in near-infrared region of spectrum, its parameters depend substantially on the presence of methyl iodide due to its external effect of heavy atom in solutions. Quantum yields of photosensitized formation of singlet oxygen were determined by the relative luminescence method.
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19 F MRI is a unique technique for tracking and quantifying the indicator (19 F-MRI label) inâ vivo without the use of ionizing radiation. Here we report new 19 F-MRI labels, which are compounds with perfluoro-tert-butyl groups: 1,2-bis(perfluoro-tert-butoxy)ethane (C10 F18 H4 O2 ) and 1,3-bis(perfluoro-tert-butyl)propane (C11 F18 H6 ). Both substances contain 18â equivalent 19 F atoms, constituting 68.67 % and 71.25 % of the molecule, respectively. The emulsions with 19 F molecules were prepared and used in 19 F MRI studies in laboratory rats inâ vivo. The substances demonstrated high contrast properties, good biological inertness and the ability to be rapidly eliminated from the body. We showed that at a dose of 0.34â mg/g of body weight in rats, the time for complete elimination of C10 F18 H4 O2 and C11 F18 H6 is â¼30â days. The results turned out to be promising for the use of the presented compounds in 19 F MRI applications, especially since they are quite easy to synthesize.
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Flúor , Imagen por Resonancia Magnética , Ratas , AnimalesRESUMEN
PURPOSE: To demonstrate the feasibility of using octafluorocyclobutane (OFCB, c-C4 F8 ) for T1 mapping of lungs in 19 F MRI. METHODS: The study was performed at 7 T in three healthy rats and three rats with pulmonary hypertension. To increase the sensitivity of 19 F MRI, a bent-shaped RF coil with periodic metal strips structure was used. The double flip angle method was used to calculate normalized transmitting RF field (B1n + ) maps and for correcting T1 maps built with the variable flip angle (VFA) method. The ultrashort TE pulse sequence was applied for acquiring MR images throughout the study. RESULTS: The dependencies of OFCB relaxation times on its partial pressure in mixtures with oxygen, air, helium, and argon were obtained. T1 of OFCB linearly depended on its partial pressure with the slope of about 0.35 ms/kPa in the case of free diffusion. RF field inhomogeneity leads to distortion of T1 maps built with the VFA method, and therefore to high standard deviation of T1 in these maps. To improve the accuracy of the T1 maps, the B1n + maps were applied for VFA correction. This contributed to a 2-3-fold decrease in the SD of T1 values in the corresponding maps compared with T1 maps calculated without the correction. Three-dimensional T1 maps were obtained, and the mean T1 in healthy rat lungs was 35 ± 10 ms, and in rat lungs with pulmonary hypertension - 41 ± 9 ms. CONCLUSION: OFCB has a spin-rotational relaxation mechanism and can be used for 19 F T1 mapping of lungs. The calculated OFCB maps captured ventilation defects induced by edema.
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Hipertensión Pulmonar , Ratas , Animales , Imagen por Resonancia Magnética/métodos , Pulmón/diagnóstico por imagen , Fantasmas de ImagenRESUMEN
PURPOSE: The aim of this study was to demonstrate the feasibility of fluorine-19 (19 F) MRI of the human lungs using octafluorocyclobutane (OFCB, C4 F8 ). This gas has 8 magnetically equivalent fluorine nuclei and relatively long T1 and T2 (Ë50 ms), which render it suitable as an MRI contrast agent. Previous experiments in small laboratory animals showed that OFCB could be successfully used as an alternative to the gases often used for 19 F MRI (sulfur hexafluoride and perfluoropropane). METHODS: One male volunteer participated in this study. Immediately before an MRI scan, the volunteer inhaled the gas mixture-80% OFCB with 20% oxygen-and held his breath. Experiments were performed on a 0.5T whole-body MR scanner with a customized transmit-receive coil tuned at 19 F frequency. Fast spin echo in 2D and 3D modes was used for image acquisition. 2D images were obtained with in-plane resolution of 10 × 10 mm2 without slice selection. 3D images were obtained with the voxel size of 10 × 10 × 30 mm2 . Breath-hold duration was 20 s for 2D and 40 s for 3D imaging, respectively. RESULTS: Anatomically consistent 19 F MR images of the human lungs were obtained with SNR around 50 in 2D mode and 20 in 3D mode. 3D volumetric images of the lungs were reconstructed and provided physiologically reasonable volume estimates. CONCLUSION: The application of OFCB enables informative 19 F lung imaging even at low magnetic field strengths. The OFCB gas shows promise as an inhalable contrast agent for fluorine lung MRI and has a potential for clinical translation.
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Pulmón , Imagen por Resonancia Magnética , Animales , Clorofluorocarburos , Medios de Contraste , Humanos , Imagenología Tridimensional , Pulmón/diagnóstico por imagen , MasculinoRESUMEN
OBJECTIVE: To identify the technical aspects of the potential use of clinically approved perfluorodecalin (PFD, C10F18) for 19F magnetic resonance imaging (MRI) oximetry method at high magnetic field 7.05 T. MATERIALS AND METHODS: 19F T1 measurements were made on a set of PFD samples with different oxygen contents (0%, 21%, and 100%) at room (21 °C) and body temperature (37 °C). In vivo MRI studies were carried out on one healthy rat and two rats with C6 brain glioma. RESULTS: The selective excitation of the magnetically equivalent 19F nuclei of CF2 groups of trans-isomer of PFD, which give a doublet at a frequency of about - 140 ppm (in relation the chemical shift of trifluoroacetic acid, which is - 76.55 ppm) should be done for correct implementation of 19F MRI oximetry method. The amount of PFD equal to 30 µl is the optimal for obtaining reliable data on the measured T1 values. In this case, the standard deviation of T1 does not exceed 5%. In vivo MRI studies showed that the values of the partial pressure of oxygen (pO2) decrease from normal values of about 38 mmHg (healthy brain) to almost 0 mmHg at the last stage of tumor growth. CONCLUSION: The study showed the feasibility of the successful application of PFD for 19F MRI oximetry method.
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Neoplasias Encefálicas/diagnóstico por imagen , Flúor/química , Fluorocarburos/química , Glioma/diagnóstico por imagen , Oximetría/métodos , Animales , Línea Celular Tumoral , Isótopos/química , Campos Magnéticos , Imagen por Resonancia Magnética , Masculino , Oxígeno , Fantasmas de Imagen , Ratas , Ratas WistarRESUMEN
Nanostructures based on buried interfaces and heterostructures are at the heart of modern semiconductor electronics as well as future devices utilizing spintronics, multiferroics, topological effects, and other novel operational principles. Knowledge of electronic structure of these systems resolved in electron momentum k delivers unprecedented insights into their physics. Here we explore 2D electron gas formed in GaN/AlGaN high-electron-mobility transistor heterostructures with an ultrathin barrier layer, key elements in current high-frequency and high-power electronics. Its electronic structure is accessed with angle-resolved photoelectron spectroscopy whose probing depth is pushed to a few nanometers using soft-X-ray synchrotron radiation. The experiment yields direct k-space images of the electronic structure fundamentals of this system-the Fermi surface, band dispersions and occupancy, and the Fourier composition of wavefunctions encoded in the k-dependent photoemission intensity. We discover significant planar anisotropy of the electron Fermi surface and effective mass connected with relaxation of the interfacial atomic positions, which translates into nonlinear (high-field) transport properties of the GaN/AlGaN heterostructures as an anisotropy of the saturation drift velocity of the 2D electrons.
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PURPOSE: To evaluate visual and surgical outcomes of cataract surgery in eyes with a history of iodine-125 (I125) brachytherapy for ocular melanoma. SETTING: Department of Ophthalmology, David Geffen School of Medicine at UCLA and the Stein Eye Institute, Los Angeles, California, USA. DESIGN: Retrospective case series. METHODS: Patients with ocular melanoma treated by I125 brachytherapy who subsequently had cataract surgery were evaluated. The recorded data included tumor size, location, preoperative ocular comorbidities, corrected distance visual acuity (CDVA), operative complications, and brachytherapy-related maculopathy before and after surgery. RESULTS: Thirty-two eyes of 32 patients were included. The mean age at the time of cataract surgery was 66.1 years. The median follow-up was 53.5 months. There were no intraoperative complications. Eighteen eyes (56.3%) had a history of preoperative radiation retinopathy, 10 involving the macula. Between 2 weeks and 4 weeks postoperatively, 22 eyes (68.8%) had an improvement in CDVA (≥2 lines). Seven of 10 eyes that failed to improve had radiation maculopathy. By the last follow-up examination, 13 eyes (40.6%) had improved CDVA, 9 eyes (28.1%) were worse (≥2 lines), and 10 eyes (31.3%) were unchanged (within ±1 line). Of 15 eyes that lost CDVA gains achieved between 2 weeks and 4 weeks postoperatively, 9 eyes had new-onset or worsening maculopathy. Cataract surgery had no effect on local tumor control or distant metastasis. CONCLUSIONS: Cataract surgery after I125 brachytherapy for ocular melanoma improved CDVA in most eyes during the immediate postoperative period. Gains were often lost with further follow-up. Progression of radiation maculopathy was primarily responsible for subsequent visual decline.
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Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Implantación de Lentes Intraoculares/métodos , Melanoma/radioterapia , Facoemulsificación/métodos , Neoplasias de la Úvea/radioterapia , Anciano , Catarata/complicaciones , Catarata/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Presión Intraocular/fisiología , Complicaciones Intraoperatorias , Masculino , Melanoma/patología , Persona de Mediana Edad , Complicaciones Posoperatorias , Seudofaquia/fisiopatología , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Úvea/patología , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Hypoxia renders tumor cells refractory to treatment. One way to overcome this problem is the design of drug delivery systems that contain the antitumor agent within an oxygen supply medium. OBJECTIVE: to evaluate whether the perfluorocarbon liquids (capable of retaining up to 50% v/v amounts of O2 gas) can be tools for delivery of photosensitizers to hypoxic tumors. METHOD: We synthesized a series of compounds in which fluoroaliphatic or fluoroaromatic moieties were conjugated to the porphyrin ring in meso-positions. Two derivatives were tested as the solutions prepared either from a dimethylformamide stock ('free' formulation) or from a perfluorocarbon emulsion in which the photosensitizer is entrapped in the oxygenated medium. RESULTS: In the emulsion the hydrophobic photosensitizer and the gas transporting liquid represented a biocompatible composition. Free formulations or perfluorocarbon emulsions of fluorinated porphyrins evoked little-to-null dark cytotoxicity. In contrast, each formulation triggered cell death upon light activation. Photodamage in the presence of fluorinated porphyrins was achievable not only at normoxic (20.9% O2 v/v) conditions but also in hypoxia (0.5% O2). With new compounds dissolved in the medium the cell photodamage in hypoxia was negligible whereas a significant photodamage was achieved with the emulsions of fluorinated porphyrins. The derivative with the fluoroalkyl substituent was more potent than its structurally close analog carrying the fluoroaryl moiety. CONCLUSION: Our new fluorinated porphyrin derivatives, especially their emulsions in which the photosensitizer and the oxygenated medium are coupled into one phase, can be perspective for photoelimination of hypoxic tumor cells.
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Antineoplásicos/farmacología , Materiales Biocompatibles/farmacología , Hidrocarburos Fluorados/farmacología , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Hidrocarburos Fluorados/síntesis química , Hidrocarburos Fluorados/química , Hipoxia/metabolismo , Estructura Molecular , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Porfirinas/química , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Electronic structure of a molecular beam epitaxy-grown system of (In,Mn)As quantum dots (QDs) buried in GaAs is explored with soft-x-ray angle-resolved photoelectron spectroscopy (ARPES) using photon energies around 1 keV. This technique, ideally suited for buried systems, extends the momentum-resolving capabilities of conventional ARPES with enhanced probing depth as well as elemental and chemical state specificity achieved with resonant photoexcitation. The experimental results resolve the dispersive energy bands of the GaAs substrate buried in â¼2 nm below the surface, and the impurity states (ISs) derived from the substitutional Mn atoms in the (In,Mn)As QDs and oxidized Mn atoms distributed near the surface. An energy shift of the Mn ISs in the QDs compared to (In,Mn)As DMS is attributed to the band offset and proximity effect at the interface with the surrounding GaAs. The absence of any ISs in the vicinity of the VBM relates the electron transport in (In,Mn)As QDs to the prototype (In,Mn)As diluted magnetic semiconductor. The SX-ARPES results are supported by measurements of the shallow core levels under variation of probing depth through photon energy. X-ray absorption measurements identify significant diffusion of interstitial Mn atoms out of the QDs towards the surface, and the role of magnetic circular dichroism is to block the ferromagnetic response of the (In,Mn)As QDs. Possible routes are drawn to tune the growth procedure aiming at practical applications of the (In,Mn)As based systems.
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Some heavy fermion materials show so-called hidden-order phases which are invisible to many characterization techniques and whose microscopic origin remained controversial for decades. Among such hidden-order compounds, CeB6 is of model character due to its simple electronic configuration and crystal structure. Apart from more conventional antiferromagnetism, it shows an elusive phase at low temperatures, which is commonly associated with multipolar order. Here we show that this phase roots in a Fermi surface instability. This conclusion is based on a full 3D tomographic sampling of the electronic structure by angle-resolved photoemission and comparison with inelastic neutron scattering data. The hidden order is mediated by itinerant electrons. Our measurements will serve as a paradigm for the investigation of hidden-order phases in f-electron systems, but also generally for situations where the itinerant electrons drive orbital or spin order.
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Cerio/química , Electrones , Hidróxidos/química , Neutrones , Cristalización , Magnetismo , Modelos Químicos , Temperatura , Tomografía Computarizada por Rayos XRESUMEN
Quasicrystals (QCs) are intermetallic alloys that have excellent long-range order but lack translational symmetry in at least one dimension. The valence band electronic structure near the Fermi energy EF in such materials is of special interest since it has a direct relation to their unusual physical properties. However, the Fermi surface (FS) topology as well as the mechanism of QC structure stabilization are still under debate. Here we report the first observation of the three-dimensional FS and valence band dispersions near EF in decagonal Al70Ni20Co10 (d-AlNiCo) QCs using soft X-ray angle-resolved photoemission spectroscopy. We show that the FS, formed by dispersive Al sp-states, has a multicomponent character due to a large contribution from high-order bands. Moreover, we discover that the magnitude of the gap at the FS related to the interaction with Brillouin zone boundary (Hume-Rothery gap) critically differs for the periodic and quasiperiodic directions.
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Electronic structure of the three-dimensional colossal magnetoresistive perovskite La(1-x)Sr(x)MnO3 has been established using soft-x-ray angle-resolved photoemission spectroscopy with its intrinsically sharp definition of three-dimensional electron momentum. The experimental results show much weaker polaronic coupling compared to the bilayer manganites and are consistent with the theoretical band structure including the empirical Hubbard parameter U. The experimental Fermi surface unveils the canonical topology of alternating three-dimensional electron spheres and hole cubes, with their shadow contours manifesting the rhombohedral lattice distortion. This picture has been confirmed by one-step photoemission calculations including displacement of the apical oxygen atoms. The rhombohedral distortion is neutral to the Jahn-Teller effect and thus polaronic coupling, but affects the double-exchange electron hopping and thus the colossal magnetoresistance effect.
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Vibrational states of the newly synthesized molecule N'-(Adamantan-2-ylidene)thiophene-2-carbohydrazide, a potential antibacterial agent, are examined experimentally for the crystalline phase and analyzed based on quantum chemical modelling of the solitary molecule and of the dimer, and assignment of the observed vibrational frequencies is proposed. Modelling of the title molecule dimer is found to describe better the experimentally observed vibration frequencies for the crystalline phase than calculations performed for a solitary molecule. Contributions from adamantane and thiophene parts within the molecule are identified. Additionally, multiple hydrogen bonds have been revealed both experimentally and computationally, inherent in the crystalline phase contrary to a solitary molecule. The spectroscopic findings correlate with the calculated interatomic distances which were found to change in the dimer versus a single molecule and to correspond better to the X-ray analysis data of the title compound in the crystalline phase.
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Antibacterianos/química , Hidrazinas/química , Modelos Moleculares , Antibacterianos/síntesis química , Hidrazinas/síntesis química , Estructura Molecular , Difracción de Rayos X/métodosRESUMEN
To study positioning of the polypeptide release factor eRF1 toward a stop signal in the ribosomal decoding site, we applied photoactivatable mRNA analogs, derivatives of oligoribonucleotides. The human eRF1 peptides cross-linked to these short mRNAs were identified. Cross-linkers on the guanines at the second, third, and fourth stop signal positions modified fragment 31-33, and to lesser extent amino acids within region 121-131 (the "YxCxxxF loop") in the N domain. Hence, both regions are involved in the recognition of the purines. A cross-linker at the first uridine of the stop codon modifies Val66 near the NIKS loop (positions 61-64), and this region is important for recognition of the first uridine of stop codons. Since the N domain distinct regions of eRF1 are involved in a stop-codon decoding, the eRF1 decoding site is discontinuous and is not of "protein anticodon" type. By molecular modeling, the eRF1 molecule can be fitted to the A site proximal to the P-site-bound tRNA and to a stop codon in mRNA via a large conformational change to one of its three domains. In the simulated eRF1 conformation, the YxCxxxF motif and positions 31-33 are very close to a stop codon, which becomes also proximal to several parts of the C domain. Thus, in the A-site-bound state, the eRF1 conformation significantly differs from those in crystals and solution. The model suggested for eRF1 conformation in the ribosomal A site and cross-linking data are compatible.
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Codón de Terminación/genética , Codón de Terminación/metabolismo , Factores de Terminación de Péptidos/metabolismo , Secuencia de Bases , Reactivos de Enlaces Cruzados , Humanos , Técnicas In Vitro , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Terminación de la Cadena Péptídica Traduccional , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Mapeo Peptídico , Factores de Terminación de Péptidos/química , Factores de Terminación de Péptidos/genética , Conformación Proteica , Estructura Terciaria de Proteína , ARN Mensajero/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Transferencia/química , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ribosomas/genética , Ribosomas/metabolismoRESUMEN
Inhibition of primer extension by ribosome-mRNA complexes (toeprinting) is a proven and powerful technique for studying mechanisms of mRNA translation. Here we have assayed an advanced toeprinting approach that employs fluorescently labeled DNA primers, followed by capillary electrophoresis utilizing standard instruments for sequencing and fragment analysis. We demonstrate that this improved technique is not merely fast and cost-effective, but also brings the primer extension inhibition method up to the next level. The electrophoretic pattern of the primer extension reaction can be characterized with a precision unattainable by the common toeprint analysis utilizing radioactive isotopes. This method allows us to detect and quantify stable ribosomal complexes at all stages of translation, including initiation, elongation and termination, generated during the complete translation process in both the in vitro reconstituted translation system and the cell lysate. We also point out the unique advantages of this new methodology, including the ability to assay sites of the ribosomal complex assembly on several mRNA species in the same reaction mixture.
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Electroforesis Capilar , Biosíntesis de Proteínas , ARN Mensajero/análisis , Ribosomas/metabolismo , Cartilla de ADN , Colorantes Fluorescentes , ARN Mensajero/metabolismo , Transcripción ReversaRESUMEN
BACKGROUND: Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS: We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE: This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread.
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Mutación/genética , Neoplasias/genética , Proteínas Supresoras de Tumor/genética , Desaminasas APOBEC-1 , Animales , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Células Clonales , Biología Computacional , Citidina Desaminasa/metabolismo , ADN Bacteriano/genética , ADN Complementario/genética , Proteínas de Escherichia coli/genética , Etiquetas de Secuencia Expresada , Efecto Fundador , Genoma/genética , Hematopoyesis/genética , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Ratones , Ratones SCID , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: With the improved median survival of kidney transplant recipients, there has been an increased focus on quality of life after transplantation. Employment is a widely recognized component of quality of life. To date, no study has demonstrated a link between post-transplant employment status and recipient and allograft survival after transplant. METHODS: The records from the United States Renal Data System (USRDS) and the United Network for Organ Sharing (UNOS) from January 1, 1995, through December 31, 2002, were examined in this retrospective study. Two outcomes, allograft survival time (time between the transplantation and allograft failure or censor) and recipient survival time (time between the transplantation and recipient death or censor), were analyzed using Cox models adjusted for potential confounding factors. RESULTS: Compared to patients working full time at the time of transplantation, those not working by choice have a greater risk to graft [hazard ratio (HR) 1.27, p < 0.001] but not to recipient survival. A similar trend was observed in patients not working at 12 months post-transplant (HR 1.30, p < 0.001 for graft survival but not for recipient survival). However, at five-yr post-transplant not working by choice was protective to the graft (HR 0.47, p < 0.01) as compared to working full time. Results of the analysis in the patient subgroups based on the comorbidities and the overall health status were similar. CONCLUSION: Employment status at the time of transplantation and in post-transplant period has a strong and independent association with the graft and recipient survival. Full time employment at the time of transplant and at one-yr post-transplant is associated with lower risk for graft failure and recipient mortality. However, working beyond the time covered by Medicare might be associated with potential risk for graft survival.
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Empleo , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Trasplante de Riñón , Adulto , Femenino , Rechazo de Injerto/cirugía , Humanos , Riñón/cirugía , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
To analyze RNA interactions with RNA binding molecules an RNA microchip containing immobilized oligoribonucleotides with protective groups [t-butyldimethylsilyl (tBDMS)] at 2'-O- positions was developed. The oligonucleotides were immobilized within three-dimensional (3-D) hydrogel pads fixed on a glass support. The protective groups preserved the oligoribonucleodes from degradation and were suitable to be removed directly on the microchip when needed, right before its use. These immobilized, deprotected oligoribonucleotides were tested for their interaction with afluorescently labeled oligodeoxyribonucleotide and analyzed for their availability to be cleaved enzymatically by the RNase binase. Stability of tBDMS-protected immobilized oligoribonucleotides after 2.5 years of storage as well as after direct RNase action was also tested. Melting curves of short RNA/DNA hybrids that had formed into gel pads of the microchip were found to exhibit clearly defined S-like shapes, with the melting temperatures in full accordance with those theoretically predicted for the same ionic strength. This approach, based on keeping the protective groups attached to oligoribonucleotides, can be applied for manufacturing any RNA microchips containing immobilized oligoribonucleotides, including microchips with two-dimensional (2-D) features. These RNA microchips can be used to measure thermodynamic parameters of RNA/RNA or RNA/DNA duplexes as well as to study ligand- or protein-RNA interactions.
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Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Oligorribonucleótidos/metabolismo , ARN/metabolismo , Secuencia de Bases , ADN/metabolismo , Endorribonucleasas/metabolismo , Colorantes Fluorescentes/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato , Cinética , Datos de Secuencia Molecular , Ácidos Nucleicos Heterodúplex , Oligorribonucleótidos/genética , TermodinámicaRESUMEN
Eukaryotic translational termination is triggered by polypeptide release factors eRF1, eRF3, and one of the three stop codons at the ribosomal A-site. Isothermal titration calorimetry shows that (i) the separated MC, M, and C domains of human eRF1 bind to eRF3; (ii) GTP binding to eRF3 requires complex formation with either the MC or M + C domains; (iii) the M domain interacts with the N and C domains; (iv) the MC domain and Mg2+ induce GTPase activity of eRF3 in the ribosome. We suggest that GDP binding site of eRF3 acquires an ability to bind gamma-phosphate of GTP if altered by cooperative action of the M and C domains of eRF1. Thus, the stop-codon decoding is associated with the N domain of eRF1 while the GTPase activity of eRF3 is controlled by the MC domain of eRF1 demonstrating a substantial structural uncoupling of these two activities though functionally they are interrelated.