RESUMEN
The concept of density-graded foams has been proposed to simultaneously enhance strain energy dissipation and the load-bearing capacities at a reduced structural weight. From a practical perspective, the fabrication of density-graded foams is often achieved by stacking different foam densities. Under such conditions, the adhesive interlayer significantly affects the mechanical performance and failure modes of the structure. This work investigates the role of different adhesive layers on the mechanical and energy absorption behaviors of graded flexible foams with distinct density layers. Three adhesive candidates with different chemical, physical, and mechanical characteristics are used to assemble density-graded polyurea foam structures. The mechanical load-bearing and energy absorption performances of the structures are evaluated under quasi-static and dynamic loading conditions. Mechanical tests are accompanied by digital image correlation (DIC) analyses to study the local strain fields developed in the vicinity of the interface. Experimental measurements are also supplemented by model predictions that reveal the interplay between the mechanical properties of an adhesive interlayer and the macroscale mechanical performance of the graded foam structures. The results obtained herein demonstrate that the deformation patterns and macroscale properties of graded foam composites can be tuned by selecting different bonding agents. It is also shown that the proper selection of an adhesive can be a practical way to address the strength-energy dissipation dichotomy in graded structures.
RESUMEN
In Pompe disease, anti-drug antibodies (ADA) to acid alpha-glucosidase (GAA) enzyme replacement therapy contribute to early mortality. Assessing individual risk for ADA development is notoriously difficult in (CRIM-positive) patients expressing endogenous GAA. The individualized T cell epitope measure (iTEM) scoring method predicts patient-specific risk of developing ADA against therapeutic recombinant human GAA (rhGAA) using individualized HLA-binding predictions and GAA genotype. CRIM-negative patients were six times more likely to develop high ADA titers than CRIM-positive patients in this retrospective study, whereas patients with high GAA-iTEM scores were 50 times more likely to develop high ADA titers than patients with low GAA-iTEM scores. This approach identifies high-risk IOPD patients requiring immune tolerance induction therapy to prevent significant ADA response to rhGAA leading to a poor clinical outcome and can assess ADA risk in patients receiving replacement therapy for other enzyme or blood factor deficiency disorders.
Asunto(s)
Anticuerpos/inmunología , Terapia de Reemplazo Enzimático , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Cadenas HLA-DRB1/genética , alfa-Glucosidasas/genética , alfa-Glucosidasas/inmunología , Simulación por Computador , Reacciones Cruzadas/inmunología , Mapeo Epitopo , Epítopos de Linfocito T/inmunología , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Humanos , Tolerancia Inmunológica/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Lactante , Metotrexato/uso terapéutico , Proteínas Recombinantes , Medición de Riesgo , Rituximab/uso terapéutico , alfa-Glucosidasas/uso terapéuticoRESUMEN
Quantum chemistry computations with a semicontinuum (cluster + continuum) solvation model have been used to cure long-standing misprediction of aqueous carbamate anion energies in the industrially important CO2 + aqueous amine reaction. Previous errors of over 10 kcal mol(-1) are revealed. Activation energies were also estimated with semicontinuum modeling, and a refined discussion of the competing hypothetical mechanisms for CO2 + monoethanolamine (MEA) is presented. Further results are also presented to demonstrate that the basicity of an amine (aqueous proton affinity) correlates only with CO2 affinity within an amine class: secondary amines have an extra CO2 affinity that primary amines do not have.
RESUMEN
Pompe disease results from inherited deficiency of the enzyme acid alpha-glucosidase resulting in lysosomal accumulation of glycogen primarily in skeletal muscle. Reported is the first case in which a donor with late onset Pompe disease (LOPD) was successfully used for deceased donor liver and kidney transplantation. This case demonstrates co-operative transplant surgery and genetic medicine evaluation and risk estimation for donors with inherited metabolic disorders some of which may be suitable for donation of selected organs for transplantation.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II , Trasplante de Riñón , Trasplante de Hígado , Donantes de Tejidos , Femenino , Humanos , Masculino , alfa-Glucosidasas/metabolismoRESUMEN
Cyclodextrin glucanotransferases (CGTases; EC 2.4.1.19) have mainly been characterized for their ability to produce cyclodextrins (CDs) from starch in an intramolecular transglycosylation reaction (cyclization). However, this class of enzymes can also catalyze intermolecular transglycosylation via disproportionation or coupling reactions onto a wide array of acceptors and could therefore be valuable as a tool for glycosylation.In this paper, we report the gene isolation, via the CODEHOP strategy, expression and characterization of a novel CGTase (CspCGT13) from a Carboxydocella sp. This enzyme is the first glycoside hydrolase isolated from the genus, indicating starch degradation via cyclodextrin production in the Carboxydocella strain. The fundamental reactivities of this novel CGTase are characterized and compared with two commercial CGTases, assayed under identical condition, in order to facilitate interpretation of the results. The comparison showed that the enzyme, CspCGT13, displayed high coupling activity using γ-CD as donor, despite preferentially forming α- and ß-CD in the cyclization reaction using wheat starch as substrate. Comparison of subsite conservation within previously characterized CGTases showed significant sequence variation in subsites -3 and -7, which may be important for the coupling activity.
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Bacterias Anaerobias/enzimología , Proteínas Bacterianas/metabolismo , Glucosiltransferasas/metabolismo , gamma-Ciclodextrinas/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Secuencia de Bases , Glucosiltransferasas/química , Glucosiltransferasas/genética , Datos de Secuencia Molecular , Unión ProteicaRESUMEN
Ab initio (coupled-cluster and density-functional) calculations of Gibbs reaction energies in solution, with new entropy-of-solvation damping terms, were performed for the ether-catalyzed hydroboration of alkenes. The goal was to test the accuracy of continuum-solvation models for reactions of neutral species in nonaqueous solvents, and the hope was to achieve an accuracy sufficient to address the mechanism in the "Pasto case": B2H6 + alkene in THF solvent. Brown's SN2/SN1 "dissociative" mechanism, of SN2 formation of borane-ether adducts followed by SN1 alkene attack, was at odds with Pasto's original SN2/SN2 hypothesis, and while Brown could prove his mechanism for a variety of cases, he could not perform the experimental test with THF adducts in THF solvent, where the higher THF concentrations might favor an SN2 second step. Two diboranes were tested: B2H6, used by Pasto, and (9BBN)2 (9BBN = 9-borabicyclo[3.3.1]nonane, C8H15B), used by Brown. The new entropy terms resulted in improved accuracy vs traditional techniques (â¼2 kcal mol(-1)), but this accuracy was not sufficient to resolve the mechanism in the Pasto case.
RESUMEN
Ab initio molecular dynamics simulations of up to 210 ps have been performed on various aqueous intermediates postulated in the CO2 + amine reaction, important for CO2 capture. Observations of spontaneous deprotonation of aqueous carbamate zwitterions R1R2NHCOO(±) by bulk water (instead of additional amine, or via umbrella sampling) are reported apparently for the first time. Carbamic acid structures R1R2NCOOH were observed in some simulations, arising from zwitterions not via classical 1,3-H-shifts but via Grotthuss-style multiple-H(+) transfer pathways that involve bulk H2O and require carbamate anions R1R2NCOO(-) as an intermediate stage along the way. H(+)-bridging complexes, including not only Zundel ions [water·H(+)·water](+) but neutral carbamate complexes [carbamate(-)·H(+)·water], were observed in simulation. These results should assist efforts in improving underlying mechanisms for kinetic modeling.
RESUMEN
BACKGROUND: Marjolin's ulcer (MU) is a rare malignancy arising from various forms of scars. This potentially fatal complication typically occurs after a certain latency period. This article attempts to reveal the importance of the latency period in the prevention and early treatment of the malignancy. METHODS: A retrospective review of 17 MU patients who underwent surgical procedures between June of 2005 and December 2011 was conducted. Etiology of injuries, latency period, repeated ulceration, and outcomes were recorded. This observational report reveals characteristics of patients who develop MU. RESULTS: An incidence of 0.7% of MU was found amongst patients complaining of existing scars in our study; burns and trauma were the most common etiology of MU. The mean latency period was 29 years (SD = 19) and the mean post-ulceration period was 7 years (SD = 9). Statistical analysis revealed a negative correlation between the age of patients at injury and the length of latency period (r = -0.8, P <0.01), as well as the lengths of pre-ulceration and post-ulceration periods (r = -0.7, P <0.01). CONCLUSIONS: Patients experience different lengths of pre- and post-ulceration periods during the latency period. Younger patients tend to have a longer latency period. Skin breakdown on chronic scars and chronic unhealed ulcers are two main sources of MU. MU may be preventable with a close surveillance of the ulcer during the latency period.
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Quemaduras/complicaciones , Cicatriz/fisiopatología , Neoplasias Cutáneas/cirugía , Úlcera Cutánea/complicaciones , Heridas y Lesiones/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/etiologíaRESUMEN
PURPOSE: The quadriceps angle (Q-angle) represents the angle between the vector of action of the quadriceps and the patellar tendon. An increased Q-angle has been associated with an increased risk of patellar instability, although there is disagreement on its reliability and validity as it is affected by the position of the limb and contraction of the quadriceps. Tibial tuberosity-trochlear groove distance (TT-TG) is ascertained by axial CT scanning, with an increased value associated with patellar instability. This study aimed to determine whether the Q-angle correlates with the TT-TG distance in patients with patellar instability. METHODS: Q-angles were measured in 34 knees that had previously undergone CT scanning for assessment of patellar instability. Measurements were made with the patient supine, the knee extended and the lower limbs in neutral rotation with the quadriceps relaxed and contracted. TT-TG distance was measured on CT scanning in an identical position. RESULTS: Of the 34 knees measured, 24 had symptoms of patellar instability, and 10 were normal. A significant negative correlation between relaxed Q-angle and TT-TG in all knees was demonstrated (p = 0.028). In symptomatic knees, contracted Q-angle also demonstrated a significant negative correlation with TT-TG (p = 0.037). CONCLUSIONS: If TT-TG distance is regarded as the gold standard measurement, Q-angle is not a reliable indicator of patellar instability. There is a clear need to develop methods to more fully characterise the knee and factors contributing to patellar instability. LEVEL OF EVIDENCE: II.
Asunto(s)
Inestabilidad de la Articulación/diagnóstico por imagen , Articulación de la Rodilla/anatomía & histología , Luxación de la Rótula/diagnóstico por imagen , Músculo Cuádriceps/anatomía & histología , Tibia/anatomía & histología , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Músculo Cuádriceps/diagnóstico por imagen , Tibia/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Cyclic ADP-ribose (cADP-ribose) is a putative second messenger or modulator. However, the role of cADP-ribose in the downstream signals of the metabotropic glutamate receptors (mGluRs) is unclear. Here, we show that glutamate stimulates ADP-ribosyl cyclase activity in rat or mouse crude membranes of retina via group III mGluRs or in superior cervical ganglion via group I mGluRs. The retina of mGluR6-deficient mice showed no increase in the ADP-ribosyl cyclase level in response to glutamate. GTP enhanced the initial rate of basal and glutamate-stimulated cyclase activity. GTP-gamma-S also stimulated basal activity. To determine whether the coupling mode of mGluRs to ADP-ribosyl cyclase is a feature common to individual cloned mGluRs, we expressed each mGluR subtype in NG108-15 neuroblastoma x glioma hybrid cells. The glutamate-induced stimulation of the cyclase occurs preferentially in NG108-15 cells over-expressing mGluRs1, 3, 5, and 6. Cells expressing mGluR2 or mGluRs4 and 7 exhibit inhibition or no coupling, respectively. Glutamate-induced activation or inhibition of the cyclase activity was eliminated after pre-treatment with cholera or pertussis toxin, respectively. Thus, the subtype-specific coupling of mGluRs to ADP-ribosyl cyclase via G proteins suggests that some glutamate-evoked neuronal functions are mediated by cADP-ribose.
Asunto(s)
ADP-Ribosil Ciclasa/metabolismo , Glioma/metabolismo , Neuroblastoma/metabolismo , Neuronas/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Retina/metabolismo , Ganglio Cervical Superior/metabolismo , ADP-Ribosil Ciclasa/química , ADP-Ribosil Ciclasa/efectos de los fármacos , Adenosina Difosfato Ribosa/biosíntesis , Animales , Membrana Celular/enzimología , Células Cultivadas , Toxina del Cólera/farmacología , Activación Enzimática/efectos de los fármacos , Glioma/química , Ácido Glutámico/farmacología , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/farmacología , Ratones , Ratones Noqueados , Neuroblastoma/química , Neuronas/química , Neuronas/citología , Ratas , Ratas Wistar , Retina/química , Retina/citología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Ganglio Cervical Superior/química , Ganglio Cervical Superior/citologíaRESUMEN
A procedure for isolation of cyclic AMP (cAMP) by thin-layer chromatography on silica gel is described. One-dimensional ascending chromatograms were developed using [H(2)O/C(2)H(5)OH/NH(4)HCO(3) (30%:70%:0.2M)] as the mobile phase. This procedure separated [32P]cAMP from other radioactive metabolites of [32P]ATP in up to 19 samples on one sheet (20 x 10 cm) over 40-60 min at room temperature (21 degrees C). This simple and rapid isolation method provides a novel and convenient technique for the assay of adenylyl cyclase.
Asunto(s)
Adenilil Ciclasas/metabolismo , AMP Cíclico/biosíntesis , Animales , Autorradiografía , Toxina del Cólera/farmacología , Cromatografía en Capa Delgada/métodos , AMP Cíclico/análisis , Glioma/metabolismo , Isoproterenol/farmacología , Marcaje Isotópico , Toxina del Pertussis/farmacología , Radioisótopos de Fósforo , Ratas , Gel de Sílice , Dióxido de Silicio/química , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
A number of routes have been suggested for the prebiotic synthesis of uracil involving the reaction of urea with malic acid, propiolic acid, cyanoacetylene and others. Cyanoacetylene has been detected in the interstellar medium as well as simulated prebiotic experiments. It is therefore plausible that dicyanoacetylene and its hydrolytic product acetylene dicarboxylic acid (ADCA) may have played a role in chemical evolution. This aspect has been examined in the present work for the synthesis of uracil from ADCA and urea reaction. It was found that when ADCA reacted with urea, uracil was formed only in the presence of phosphoric acid and phosphates. ammonium phosphates gave higher yields of uracil than other phosphates. In the absence of phosphoric acid or phosphates no uracil formation took place. This type of synthesis could have taken place in prebiotic oceans which contained ammonium phosphates and other salts.
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Acetileno/análogos & derivados , Ácidos Grasos Insaturados , Uracilo/síntesis química , Urea , Alquinos , FosfatosRESUMEN
Biochemical diagnosis of two cases of metachromatic leukodystrophy /hereditary disease was carried out by means of detection of arylsulfatase A deficiency in leukocytes of impaired children. Prenatal diagnosis of metachromatic leukodystrophy was first performed using estimation of the arylsulfatase A activity in bioptic samples of chorion in 8 week pregnancy. Development of the healthy fetus was diagnosed on the basis of detection of the normal enzymatic activity in the chorion of pregnant woman which had earlier two children with metachromatic leukodystrophy. This conclusion was confirmed by analysis of the fetal tissues in which the normal arylsulfatase A activity was found.