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BACKGROUND AND OBJECTIVES: Postpartum anaemia is a prevalent health problem. We aimed to determine the compliance rate for red blood cell (RBC) transfusion indication among postpartum women in a single tertiary care centre in Quebec, Canada. MATERIALS AND METHODS: Retrospective cohort study including all women ≥6 h postpartum who received ≥1 RBC transfusion during their delivery hospitalization between January 2005 and February 2022. We determined our centre's compliance rate by indication as compared to current society guidelines, all published after 2015 (Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis [NATA], Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG]). We then explored predictors of guideline non-compliance and described transfusion practices in our centre. RESULTS: A total of 171 women were included. Our centre's compliance rate was 79.5% (95% confidence interval [CI] 72.7-84.8). Predictors of guideline non-compliance were maternal medical comorbidity or abnormal placentation, both limited by large CIs (odds ratio [OR] 2.26, CI 1.02-4.94, p = 0.04; OR 4.00, CI 1.31-12.06, p = 0.01, respectively). Postpartum haemorrhage was diagnosed among 68% of the cohort, mostly due to uterine atony (73.3%). Mean baseline and nadir haemoglobin were 111 g/L (±18) and 62 g/L (±7.7), respectively. Multiple unit initial transfusion was found in a majority of patients (63.7%). Iron therapy was administered to 51.5% of women in-hospital and 81.9% received an oral iron prescription at discharge. There were no differences in primary or secondary outcomes subsequent to relevant guideline publication. CONCLUSION: Our centre's compliance rate for RBC transfusion indication meets current practice guidelines. Areas for improvement include single-unit initial transfusion protocols and adjuvant iron treatment. Antenatal optimization of haemoglobin and ferritin stores may limit postpartum transfusions.
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BACKGROUND: Anti-K is an alloantibody stimulated in response to the KEL1 antigen and may cause hemolytic disease of the fetus and newborn (HDFN). Provision of KEL1 negative blood to females of child-bearing potential was not our practice. We assessed the impact of our policy and assessed feasibility of a KEL1 negative transfusion policy. STUDY DESIGN AND METHODS: This is a cohort study spanning Jan 1, 2007-Jun 30, 2017 in Hamilton, Canada. Data were obtained via our institution's transfusion database. Chart reviews of females age ≤45 with anti-K were performed; data on RBC KEL1 phenotype were obtained from the blood supplier when needed to ascertain the cause of alloimmunization. Descriptive analysis of hospital KEL1 negative inventory demand and supply was performed. RESULTS: From Jan 2007-Jun 2017, 8.6% of all RBC units transfused were provided to females age ≤45. There were 111 females with detectable anti-K. Median age at time of antibody detection was 34 years (interquartile range 27-40) and 28 of 111 (25.2%) patients may have been alloimmunized by transfusion. Of 49 pregnancies, seven had complications due to anti-K. We estimated that our existing RBC inventory (with 16% units known to be KEL1 negative in 2017) is sufficient to meet demand and support a KEL1 negative transfusion policy for females age ≤45. CONCLUSION: Transfusion was responsible for alloimmunization in 25% of females with anti-K over 10 years. Analysis of supply and demand can be used to inform feasibility of a KEL1 negative transfusion policy.
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Antígenos de Grupos Sanguíneos , Eritroblastosis Fetal , Humanos , Embarazo , Femenino , Sistema del Grupo Sanguíneo de Kell/genética , Estudios de Factibilidad , Estudios de Cohortes , Isoanticuerpos , Eritroblastosis Fetal/prevención & control , EritrocitosRESUMEN
BACKGROUND AND OBJECTIVES: A high proportion of suspected weak D patients referred to Héma-Québec were genotyped as weak D type 42 (368/2105, 17.5%). These patients are currently considered D with regard to RhD immunoprophylaxis in pregnancy and transfusion. The goal of this study was to retrospectively evaluate the risk of alloimmunization in weak D type 42 patients and to characterize their RhD surface molecule expression on red blood cells (RBCs) in comparison to other weak D types (1, 2 and 3). MATERIALS AND METHODS: A retrospective analysis using the weak D type 42 patients' medical data to verify potential anti-D alloimmunization events was conducted. Quantitative analyses using flow cytometry were also performed on RBCs to quantify the cell surface density of the D antigen. RESULTS: Data on 215 subjects with weak D type 42 were reviewed. None developed immune allo-anti-D; three had definite exposure to D+ red cells and 41 had possible exposure through pregnancy. Flow cytometry analysis showed that weak D types 1, 2, 3 and 42 had relative antigen densities of 2.7%, 2.2%, 8.1% and 3.6%, respectively, with R1R2 red cells referencing 100% density. The estimated antigen density range of weak D type 42 was 819-1104 sites per RBC. CONCLUSION: Our retrospective alloimmunization data analysis and antigen density study establish a basis for the consideration of a weak D type 42 individual as D+. This consideration would allow for a targeted reduction of RhD immunoprophylaxis in pregnancy and the unjustified use of D- units for transfusion.
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Transfusión Sanguínea , Sistema del Grupo Sanguíneo Rh-Hr , Eritrocitos/metabolismo , Femenino , Humanos , Isoanticuerpos , Embarazo , Quebec , Estudios RetrospectivosRESUMEN
We study the size-dependent optical properties of periodic arrays of semiconducting nanolines in the near-infrared to near-ultraviolet spectral range, where the absorption of the semiconductor increases. Using band structure calculations, we demonstrate that specific dimensions allow the slow down of the light, resulting in an enhanced absorption as compared to bulk material once the extinction coefficient of the semiconductor becomes comparable to its refractive index. Further, the refractive properties of the arrays can be tailored beyond the values of the constituting materials when the extinction coefficient of the semiconductor exceeds its refractive index. To confirm our theoretical findings, we propose a simple semi-analytical model for the light interactions with such structures and validate it with experimental reflectance spectra collected on arrays for the next-generation transistors.
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p53 as an effector of nucleolar stress is well defined, but p53 independent mechanisms are largely unknown. Like p53, the NF-κB transcription factor plays a critical role in maintaining cellular homeostasis under stress. Many stresses that stimulate NF-κB also disrupt nucleoli. However, the link between nucleolar function and activation of the NF-κB pathway is as yet unknown. Here we demonstrate that artificial disruption of the PolI complex stimulates NF-κB signalling. Unlike p53 nucleolar stress response, this effect does not appear to be linked to inhibition of rDNA transcription. We show that specific stress stimuli of NF-κB induce degradation of a critical component of the PolI complex, TIF-IA. This degradation precedes activation of NF-κB and is associated with increased nucleolar size. It is mimicked by CDK4 inhibition and is dependent upon a novel pathway involving UBF/p14ARF and S44 of the protein. We show that blocking TIF-IA degradation blocks stress effects on nucleolar size and NF-κB signalling. Finally, using ex vivo culture, we show a strong correlation between degradation of TIF-IA and activation of NF-κB in freshly resected, human colorectal tumours exposed to the chemopreventative agent, aspirin. Together, our study provides compelling evidence for a new, TIF-IA-NF-κB nucleolar stress response pathway that has in vivo relevance and therapeutic implications.
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Nucléolo Celular/metabolismo , FN-kappa B/metabolismo , Proteínas del Complejo de Iniciación de Transcripción Pol1/metabolismo , Estrés Fisiológico , Transporte Activo de Núcleo Celular , Línea Celular , Línea Celular Tumoral , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Humanos , Proteínas del Complejo de Iniciación de Transcripción Pol1/química , ARN Polimerasa I/metabolismo , Serina/metabolismo , Transducción de Señal , Factor de Transcripción ReIA/metabolismo , Proteína p14ARF Supresora de Tumor/fisiologíaRESUMEN
BACKGROUND: The efficacy of premedication for the prevention of nonhemolytic transfusion reactions remains controversial. This systematic review and meta-analysis assessed the effect of premedication on the rate of nonhemolytic transfusion reactions after allogeneic blood transfusion. STUDY DESIGN AND METHODS: We searched the literature using CENTRAL, MEDLINE, EMBASE, ISI Web of Science, and clinicaltrials.gov databases from inception until October 31, 2018. We included all randomized controlled trials comparing premedication to placebo or no treatment in patients receiving any labile blood product. Outcome measures were reported as relative risks (RRs) with 95% confidence intervals (CIs). Data were combined for similar outcomes where appropriate using a random-effects model. Analyses were done at both the patient and transfusion level. RESULTS: Three randomized trials using acetaminophen and antihistamine as premedication met the inclusion criteria. A total of 517 patients received 4444 red blood cell or platelet transfusions. Pooled patient-level estimates with premedication for all nonhemolytic, febrile nonhemolytic, and minor allergic reactions were RR, 0.92 (95% CI, 0.63-1.35); RR, 0.54 (95% CI, 0.26-1.1); and RR, 1.37 (95% CI 0.81-2.31), respectively. Transfusion-level analyses also showed no benefit with premedication. Of 517 patients randomized, only 27 (5.2%) had a history of transfusion reactions. CONCLUSION: Routine premedication with acetaminophen and antihistamines did not prevent nonhemolytic transfusion reactions; however, the estimate of effect was greatest for febrile reactions. The impact of premedication in patients with a prior history of transfusion reactions remains unknown and requires further evaluation in future clinical trials.
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Premedicación/métodos , Reacción a la Transfusión/prevención & control , Acetaminofén/uso terapéutico , Transfusión Sanguínea , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Transfusion-associated anaphylaxis has been associated with anti-immunoglobulin A (anti-IgA) of IgG class in patients with IgA deficiency. In recent years, however, the frequency and clinical impact of this syndrome has been questioned. We present a case of recurrent red blood cell (RBC) transfusion-associated anaphylactoid reactions (rigors, hypertension, transient monocytopenia, and neutropenia) associated with anti-IgA. CASE REPORT: An 88-year-old woman developed anemia after a traumatic right humerus fracture. After receiving approximately 100 mL of RBCs she developed rigors and hypertension; her absolute neutrophil and monocyte counts decreased by 73 and 100%, respectively. All symptoms and signs resolved, and her blood counts normalized. A second RBC transfusion was given, with recurrence of rigors, hypertension, neutropenia, and monocytopenia (69 and 100% declines, respectively), along with fever. All tests for hemolysis were negative. She then received two transfusions of washed RBCs, without incident. The patient was found to be deficient in IgA (<0.05 mg/dL). Further, anti-IgA of IgG class antibodies were detected in high levels by enzyme-linked immunosorbent assay (>1000 U/mL). We reviewed case reports, case series, and reviews of IgA deficiency-associated reactions, examining whether hypertensive reactions and acute neutropenia and/or monocytopenia have been associated with anti-IgA reactions. RESULTS: Reports of reactions associated with anti-IgA emphasize hypotension and are generally classified as "anaphylactic or anaphylaxis." No previous reports described neutropenia or monocytopenia. CONCLUSION: Our case suggests that adverse transfusion reactions associated with anti-IgA of IgG class may sometimes be characterized by anaphylactoid features such as rigors and hypertension, with transient monocytopenia and neutropenia.
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Anafilaxia/etiología , Anticuerpos Antiidiotipos/sangre , Transfusión de Eritrocitos/efectos adversos , Deficiencia de IgA , Neutropenia/etiología , Reacción a la Transfusión , Anciano de 80 o más Años , Anafilaxia/complicaciones , Anemia/etiología , Femenino , Humanos , Monocitos/patología , Pancitopenia , RecurrenciaRESUMEN
The objectives of this study were (1) to assess the effect of a denatured whey protein concentrate (DWPC) and its fractions on cheese yield, composition, and rheological properties, and (2) to separate the direct effect of the DWPC or its fractions on cheese rheological properties from the effect of a concomitant increase in cheese moisture. Semihard cheeses were produced at a laboratory scale, and mechanical properties were characterized by dynamic rheometry. Centrifugation was used to induce a moisture gradient in cheese to separate the direct contribution of the DWPC from the contribution of moisture to cheese mechanical properties. Cheese yield increased and complex modulus (G*) decreased when the DWPC was substituted for milk proteins in milk. For cheeses with the same moisture content, the substitution of denatured whey proteins for milk proteins had no direct effect on rheological parameters. The DWPC was fractionated to evaluate the contribution of its different components (sedimentable aggregates, soluble component, and diffusible component) to cheese yield, composition, and rheological properties. The sedimentable aggregates were primarily responsible for the increase in cheese yield when DWPC was added. Overall, moisture content explained to a large extent the variation in cheese rheological properties depending on the DWPC fraction. However, when the effect of moisture was removed, the addition of the DWPC sedimentable fraction to milk increased cheese complex modulus. Whey protein aggregates were hypothesized to act as active fillers that physically interact with the casein matrix and confer rigidity after pressing.
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Queso/análisis , Manipulación de Alimentos/métodos , Leche/química , Reología , Proteína de Suero de Leche/química , Animales , Caseínas , Tecnología de Alimentos , Proteínas de la Leche , Desnaturalización ProteicaRESUMEN
Nucleolar sequestration of the RelA subunit of nuclear factor (NF)-κB is an important mechanism for regulating NF-κB transcriptional activity. Ubiquitylation, facilitated by COMMD1 (also known as MURR1), acts as a crucial nucleolar-targeting signal for RelA, but how this ubiquitylation is regulated, and how it differs from cytokine-mediated ubiquitylation, which causes proteasomal degradation of RelA, is poorly understood. Here, we report a new role for p300 (also known as EP300) in controlling stimulus-specific ubiquitylation of RelA, through modulation of COMMD1. We show that p300 is required for stress-mediated ubiquitylation and nucleolar translocation of RelA, but that this effect is indirect. We also demonstrate that COMMD1 is acetylated by p300 and that acetylation protects COMMD1 from XIAP-mediated proteosomal degradation. Furthermore, we demonstrate that COMMD1 acetylation is enhanced by aspirin-mediated stress, and that this acetylation is absolutely required for the protein to bind RelA under these conditions. In contrast, tumour necrosis factor (TNF) has no effect on COMMD1 acetylation. Finally, we demonstrate these findings have relevance in a whole tissue setting. These data offer a new paradigm for the regulation of NF-κB transcriptional activity, and the multiple other pathways controlled by COMMD1.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Factor de Transcripción ReIA/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Acetilación , Nucléolo Celular/metabolismo , Células Cultivadas , Humanos , Procesamiento Proteico-Postraduccional/fisiología , Subunidades de Proteína/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ubiquitinación/fisiologíaAsunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Inmunoglobulinas Intravenosas/uso terapéutico , Trombocitopenia/prevención & control , Autoanticuerpos/sangre , Arteria Femoral/cirugía , Humanos , Masculino , Persona de Mediana Edad , Activación Plaquetaria/inmunología , Trombocitopenia/inducido químicamente , Trombocitopenia/inmunología , Trombosis/tratamiento farmacológicoAsunto(s)
ADP Ribosa Transferasas/genética , Codón sin Sentido , Proteínas de la Membrana/genética , ADP Ribosa Transferasas/inmunología , Adolescente , Alelos , Tipificación y Pruebas Cruzadas Sanguíneas , ADN Complementario/genética , Femenino , Mutación del Sistema de Lectura , Hemofilia A/complicaciones , Humanos , Isoanticuerpos/sangre , Articulación de la Rodilla/cirugía , Masculino , Proteínas de la Membrana/inmunología , Padres , Fenotipo , Mutación Puntual , Eliminación de Secuencia , SiriaRESUMEN
Successful early attrition of potential problematic compounds is of great importance in the pharmaceutical industry. The lead compound in a recent project targeting neuropathic pain was susceptible to metabolic bioactivation, which produced reactive metabolites and showed covalent binding to protein. Therefore, as a part of the backup series for this compound several structural modifications were explored to mediate the reactive metabolite and covalent binding risk. A homomorpholine containing series of compounds was identified without compromising potency. However, when these compounds were incubated with human liver microsomes in the presence of GSH, Cys-Gly adducts were identified, instead of intact GSH conjugates. This article examines the formation of the Cys-Gly adduct with AZX ([M+H]+ 486) as a representative compound for this series. The AZX-Cys-Gly-adduct ([M+H]+ 662) showed evidence of ring contraction by formation of a thiazolidine-glycine and was additionally shown to be unstable. During its isolation for structural characterization by 1H NMR spectroscopy, it was found to have decomposed to a product with [M+H]+ 446. The characterization and identification of this labile GSH-derived adduct using LC-MS/MS and 1H NMR are described, along with observations around stability. In addition, various structurally related trapping reagents were employed in an attempt to further investigate the reaction mechanism along with a methoxylamine trapping experiment to confirm the structure of the postulated reactive intermediate.
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Morfolinas/metabolismo , Tiazolidinas/química , Tiazolidinas/metabolismo , Bacillus megaterium/enzimología , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Estructura Molecular , Morfolinas/químicaRESUMEN
The first-line treatment of glioblastoma typically consists of a maximal surgical resection, followed by a combination of radio-chemotherapy with temozolomide. There is however no consensus regarding optimal therapeutic approaches at relapse. The following phase II study explored the therapeutic gain obtained when exposing these patients to a combination of intra-arterially administered carboplatin and melphalan at first or second relapse as a salvage treatment in recurrent glioblastoma. Fifty-one consecutive patients diagnosed with glioblastoma were accrued and offered this treatment at first or second relapse. A Karnofsky score of ≥ 60 was required, and when appropriate, patients were first reoperated prior to accrual. Patients enrolled were treated every 4 weeks (1 cycle) for up to 12 cycles. Progression was evaluated by Macdonald criteria. Primary end point surrogates were overall survival from diagnosis and study entry. Median survival from diagnosis and study entry was 23 and 11 months, respectively. The median time to progression was 5.2 months. All patients enrolled were treated for a minimum of 2 cycles. Hematologic toxicity was manageable, with an 8 % of grade II neutropenia, 12 % of grade II thrombocytopenia and 7 % of grade III thrombocytopenia. This therapeutic strategy represents an adequate option in the second-line treatment of recurrent glioblastoma. The adjunction of an osmotic permeabilization could be considered to further expand delivery, and hopefully improve survival in these patients.
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Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Carboplatino/administración & dosificación , Glioblastoma/tratamiento farmacológico , Terapia Recuperativa/métodos , Adulto , Anciano , Antineoplásicos/efectos adversos , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Carboplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Glioblastoma/diagnóstico , Glioblastoma/patología , Humanos , Infusiones Intraarteriales , Estimación de Kaplan-Meier , Estado de Ejecución de Karnofsky , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Terapia Recuperativa/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Recently, a step-flow growth mode has been proposed to break the inherent molybdenum disulfide (MoS2) crystal domain bimodality and yield a single-crystalline MoS2 monolayer on commonly employed sapphire substrates. This work reveals an alternative growth mechanism during the metal-organic chemical vapor deposition (MOCVD) of a single-crystalline MoS2 monolayer through anisotropic 2D crystal growth. During early growth stages, the epitaxial symmetry and commensurability of sapphire terraces rather than the sapphire step inclination ultimately govern the MoS2 crystal orientation. Strikingly, as the MoS2 crystals continue to grow laterally, the sapphire steps transform the MoS2 crystal geometry into diamond-shaped domains presumably by anisotropic diffusion of ad-species and facet development. Even though these MoS2 domains nucleate on sapphire with predominantly bimodal 0 and 60° azimuthal rotation, the individual domains reach lateral dimensions of up to 200 nm before merging seamlessly into a single-crystalline MoS2 monolayer upon coalescence. Plan-view transmission electron microscopy reveals the single-crystalline nature across 50 µm by 50 µm inspection areas. As a result, the median carrier mobility of MoS2 monolayers peaks at 25 cm2 V-1 s-1 with the highest value reaching 28 cm2 V-1 s-1. This work details synthesis-structure correlations and the possibilities to tune the structure and material properties through substrate topography toward various applications in nanoelectronics, catalysis, and nanotechnology. Moreover, shape modulation through anisotropic growth phenomena on stepped surfaces can provide opportunities for nanopatterning for a wide range of materials.
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Introduction: Compared to judokas (JU) and non-athletes (NA), horseback riders (HR) may develop specific changes in their sensory control of balance. Methods: Thirty-four international-level JU, twenty-seven international-level HR and twenty-one NA participated. Participants stood upright on a plateform (static condition) or on a seesaw device with an instability along the mediolateral (ML) or the anteroposterior (AP) direction (dynamic conditions). These conditions were carried out with eyes opened (EO) or closed (EC), and with (wF) or without a foam (nF). Experimental variables included conventional (linear), non-linear center-of-pressure (COP) parameters, Romberg Quotient (RQ) and Plantar Quotient (PQ). Results: Group effects. COP Surface (COPS) and standard deviation of COP along AP (SDY) were lower in HR than in JU in Static. SD Y was lower in HR than in JU in Dynamic AP. COP velocity (COPV) was lower in both HR and JU than in NA in Static and Dynamic. Sample entropy along AP and ML (SampEnY and SampEnX) were higher in HR than in JU in Static. SampEnY was higher in HR than in JU in Dynamic ML. Sensory effects. In EC, COPV was lower in JU than in NA in Dynamic AP, and lower in JU than in both HR and NA in Dynamic ML. In EO, COPV was lower in both JU and HR than in NA in Dynamic ML. RQ applied to COPS was lower in JU than in both HR and NA in Dynamic AP, and lower in JU than in HR in Dynamic ML. RQ applied to COPV was lower in JU than in both HR and NA in Static and Dynamic. PQ applied to COPS was higher in JU than in both HR and NA in Dynamic ML. Conclusion: Results showed that the effects of sport expertise on postural control could only be revealed with specific COP variables and were directionally oriented and sport-dependant. HR seem to rely more on vision than JU, thus revealing that the contribution of the sensory inputs to balance control is also sport-dependent. Results open up new knowledge on the specificity of sport practice on multisensory balance information during upright posture.
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Rational creation of polymeric semiconductors from novel building blocks is critical to polymer solar cell (PSC) development. We report a new series of bithiopheneimide-based donor-acceptor copolymers for bulk-heterojunction (BHJ) PSCs. The bithiopheneimide electron-deficiency compresses polymer bandgaps and lowers the HOMOs--essential to maximize power conversion efficiency (PCE). While the dithiophene bridge progression R(2)SiâR(2)Ge minimally impacts bandgaps, it substantially alters the HOMO energies. Furthermore, imide N-substituent variation has negligible impact on polymer opto-electrical properties, but greatly affects solubility and microstructure. Grazing incidence wide-angle X-ray scattering (GIWAXS) indicates that branched N-alkyl substituents increased polymer π-π spacings vs linear N-alkyl substituents, and the dithienosilole-based PBTISi series exhibits more ordered packing than the dithienogermole-based PBTIGe analogues. Further insights into structure-property-device performance correlations are provided by a thieno[3,4-c]pyrrole-4,6-dione (TPD)-dithienosilole copolymer PTPDSi. DFT computation and optical spectroscopy show that the TPD-based polymers achieve greater subunit-subunit coplanarity via intramolecular (thienyl)S···O(carbonyl) interactions, and GIWAXS indicates that PBTISi-C8 has lower lamellar ordering, but closer π-π spacing than does the TPD-based analogue. Inverted BHJ solar cells using bithiopheneimide-based polymer as donor and PC(71)BM as acceptor exhibit promising device performance with PCEs up to 6.41% and V(oc) > 0.80 V. In analogous cells, the TPD analogue exhibits 0.08 V higher V(oc) with an enhanced PCE of 6.83%, mainly attributable to the lower-lying HOMO induced by the higher imide group density. These results demonstrate the potential of BTI-based polymers for high-performance solar cells, and provide generalizable insights into structure-property relationships in TPD, BTI, and related polymer semiconductors.
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In order to improve the performance of today's nanoscaled semiconductor devices, characterization techniques that can provide information about the position and activity of dopant atoms and the strain fields are essential. Here we demonstrate that by using a modern transmission electron microscope it is possible to apply multiple techniques to advanced materials systems in order to provide information about the structure, fields, and composition with nanometer-scale resolution. Off-axis electron holography has been used to map the active dopant potentials in state-of-the-art semiconductor devices with 1 nm resolution. These dopant maps have been compared to electron energy loss spectroscopy maps that show the positions of the dopant atoms. The strain fields in the devices have been measured by both dark field electron holography and nanobeam electron diffraction.
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Análisis de Falla de Equipo/métodos , Microscopía Electrónica de Transmisión/métodos , Nanotecnología/métodos , Radiometría/métodos , Semiconductores , Campos ElectromagnéticosRESUMEN
In view of its epitaxial seeding capability, c-plane single crystalline sapphire represents one of the most enticing, industry-compatible templates to realize manufacturable deposition of single crystalline two-dimensional transition metal dichalcogenides (MX2) for functional, ultrascaled, nanoelectronic devices beyond silicon. Despite sapphire being atomically flat, the surface topography, structure, and chemical termination vary between sapphire terraces during the fabrication process. To date, it remains poorly understood how these sapphire surface anomalies affect the local epitaxial registry and the intrinsic electrical properties of the deposited MX2 monolayer. Therefore, molybdenum disulfide (MoS2) is deposited by metal-organic chemical vapor deposition (MOCVD) in an industry-standard epitaxial reactor on two types of c-plane sapphire with distinctly different terrace and step dimensions. Complementary scanning probe microscopy techniques reveal an inhomogeneous conductivity profile in the first epitaxial MoS2 monolayer on both sapphire templates. MoS2 regions with poor conductivity correspond to sapphire terraces with uncontrolled topography and surface structure. By intentionally applying a substantial off-axis cut angle (1° in this work), the sapphire terrace width and step height-and thus also surface structure-become more uniform across the substrate and MoS2 conducts the current more homogeneously. Moreover, these effects propagate into the extrinsic MoS2 device performance: the field-effect transistor variability reduces both within and across wafers at higher median electron mobility. Carefully controlling the sapphire surface topography and structure proves an essential prerequisite to systematically study and control the MX2 growth behavior and capture the influence on its structural and electrical properties.
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Elevated NF-κB activity is a contributory factor in many hematologic and solid malignancies. Nucleolar sequestration of NF-κB/RelA represses this elevated activity and mediates apoptosis of cancer cells. Here, we set out to understand the mechanisms that control the nuclear/nucleolar distribution of RelA and other regulatory proteins, so that agents can be developed that specifically target these proteins to the organelle. We demonstrate that RelA accumulates in intranucleolar aggresomes in response to specific stresses. We also demonstrate that the autophagy receptor, SQSTM1/p62, accumulates alongside RelA in these nucleolar aggresomes. This accumulation is not a consequence of inhibited autophagy. Indeed, our data suggest nucleolar and autophagosomal accumulation of p62 are in active competition. We identify a conserved motif at the N-terminus of p62 that is essential for nucleoplasmic-to-nucleolar transport of the protein. Furthermore, using a dominant-negative mutant deleted for this nucleolar localization signal (NoLS), we demonstrate a role for p62 in trafficking RelA and other aggresome-related proteins to nucleoli, to induce apoptosis. Together, these data identify a novel role for p62 in trafficking nuclear proteins to nucleolar aggresomes under conditions of cell stress, thus maintaining cellular homeostasis. They also provide invaluable information on the mechanisms that regulate the nuclear/nucleolar distribution of RelA that could be exploited for therapeutic purpose. IMPLICATIONS: The data open up avenues for the development of a unique class of therapeutic agents that act by targeting RelA and other aberrantly active proteins to nucleoli, thus killing cancer cells.
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FN-kappa B/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteína Sequestosoma-1/metabolismo , Apoptosis , Autofagia , Células Cultivadas , Humanos , Transducción de SeñalRESUMEN
New aromatic compounds with a pyridazine core have been synthesized. Four electron-withdrawing monomers have been easily prepared from simple condensation reactions and ring closure procedures. Optimized HOMO, LUMO, and bandgap energy levels have been obtained. The resulting conjugated polymers have been tested in organic solar cells. First studies have revealed power conversion efficiencies up to 0.5% for an active area of 1.0 cm(2) .