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BACKGROUND: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with disease progression on prior endocrine therapy. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. PATIENTS AND METHODS: MONARCH 3 is a randomized, double-blind, phase III study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival was an exploratory endpoint. RESULTS: A total of 493 women were randomized 2 : 1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease, there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% confidence interval 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed. CONCLUSIONS: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 months; subgroup with visceral disease: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Inhibidores de la Aromatasa , Bencimidazoles , Neoplasias de la Mama , Letrozol , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Método Doble Ciego , Letrozol/administración & dosificación , Letrozol/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Inhibidores de la Aromatasa/administración & dosificación , Persona de Mediana Edad , Anciano , Receptores de Progesterona/metabolismo , Receptores de Estrógenos/metabolismo , Anastrozol/uso terapéutico , Anastrozol/administración & dosificación , Adulto , Anciano de 80 o más Años , Supervivencia sin ProgresiónRESUMEN
We report on the design, manufacture, and testing of an ultra-compact telescope for 16 unit (16U) CubeSats for Earth and space observation. This telescope provides 1 arcsec resolution at a 2.9 degree field of view. Dimensions are optimized to 230 × 230 × 330mm3 with a mass of less than 6kg including support structure. Our catadioptric 5-element design consists of a full-aperture corrector, a Mangin primary mirror (PM), a secondary mirror (SM), and a 2-lens field corrector. The focal length is 745mm, and squared-circular aperture has an equivalent diameter of 241mm. The designed modulation transfer function (MTF) is 0.275 for the entire unit including baffles at a Nyquist frequency of 161 cycles/mm for the 450-800nm band. As one of the distinguishing features of our state-of-the-art design, all optical surfaces are spherical to simplify adjustment. For the best thermal stability, all optical elements are produced from fused silica. We describe the details of design, adjustment, and laboratory performance tests for space environments in accordance with the requirements for in-orbit operation onboard Earth-observation micro-satellites to be launched in 2018.
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PURPOSE: This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). METHODS: Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 µg/m2/day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. RESULTS: The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm3 and 161.75/mm3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. CONCLUSIONS: DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.
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Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Filgrastim/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Polietilenglicoles/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/etiología , Neutropenia Febril Inducida por Quimioterapia/prevención & control , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Filgrastim/efectos adversos , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Inyecciones Subcutáneas , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Taxoides/administración & dosificaciónAsunto(s)
ADN Mitocondrial/genética , Eliminación de Gen , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Adulto , Anciano , Estudios Transversales , ADN Mitocondrial/análisis , Humanos , Leucocitos , Persona de Mediana Edad , Estudios Prospectivos , República de Corea/epidemiologíaRESUMEN
We report a new and improved photon counting method for the precision PDE measurement of SiPM detectors, utilizing two integrating spheres connected serially and calibrated reference detectors. First, using a ray tracing simulation and irradiance measurement results with a reference photodiode, we investigated irradiance characteristics of the measurement instrument, and analyzed dominating systematic uncertainties in PDE measurement. Two SiPM detectors were then used for PDE measurements between wavelengths of 368 and 850 nm and for bias voltages varying from around 70V. The resulting PDEs of the SiPMs show good agreement with those from other studies, yet with an improved accuracy of 1.57% (1σ). This was achieved by the simultaneous measurement with the NIST calibrated reference detectors, which suppressed the time dependent variation of source light. The technical details of the instrumentation, measurement results and uncertainty analysis are reported together with their implications.
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Algoritmos , Fotometría/instrumentación , Fotometría/métodos , Semiconductores , Silicio/química , Silicio/efectos de la radiación , Diseño de Equipo , Análisis de Falla de Equipo , FotonesRESUMEN
BACKGROUNDS: A pegylated form of recombinant granulocyte-colony stimulating factor (G-CSF) was developed for prophylactic use in breast cancer. The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer. METHODS: A total of 61 patients receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were randomized in cycle 1 to receive daily injections of filgrastim (100 µg/m(2)) or a single subcutaneous injection of pegylated filgrastim DA-3031 at a dose of either 3.6 mg or 6 mg. RESULTS: The mean duration of grade 4 neutropenia in cycle 1 was comparable among the treatment groups (2.48, 2.20, and 2.05 days for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.275). No statistically significant differences were observed in the incidence of febrile neutropenia between the treatment groups (9.5 %, 15.0 %, and 5.0 % for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.681) in cycle 1. The incidences of adverse events attributable to G-CSF were similar among the treatment groups. CONCLUSIONS: Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.
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Biosimilares Farmacéuticos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neutropenia/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Neoplasias de la Mama/sangre , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Recuento de Leucocitos , Persona de Mediana Edad , Neutropenia/sangre , Neutropenia/inducido químicamente , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
We report on design, manufacture, and testing of a Slewing Mirror Telescope (SMT), the first of its kind and a part of Ultra-Fast Flash Observatory-pathfinder (UFFO-p) for space-based prompt measurement of early UV/optical light curves from Gamma-Ray Bursts (GRBs). Using a fast slewing mirror of 150 mm diameter mounted on a 2 axis gimbal stage, SMT can deliver the images of GRB optical counterparts to the intensified CCD detector within 1.5~1.8 s over ± 35 degrees in the slewing field of view. Its Ritchey-Chrétien telescope of 100 mm diameter provides a 17 × 17 arcmin² instantaneous field of view. Technical details of design, construction, the laboratory performance tests in space environments for this unique SMT are described in conjunction with the plan for in-orbit operation onboard the Lomonosov satellite in 2013.
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Lentes , Radiometría/instrumentación , Nave Espacial/instrumentación , Telescopios , Diseño de Equipo , Análisis de Falla de Equipo , Rayos gamma , Fotones , Rayos UltravioletaRESUMEN
Streptococcus pneumoniae (the pneumococcus) colonizes the human nasopharynx and can cause invasive disease aided by the pneumococcal capsule. Group II nontypeable S. pneumoniae (NTSp) lacks a polysaccharide capsule, and a subgroup of NTSp carriage isolates has been found to have a novel gene, pneumococcal surface protein K (pspK), which replaces the capsule locus. A recent rise in the number of NTSp isolates colonizing the human nasopharynx has been observed, but the colonization factors of NTSp have not been well studied. PspK has been shown to play a role in mouse colonization. We therefore examined PspK-mediated immune evasion along with adherence to host cells and colonization. PspK bound human secretory immunoglobulin A (sIgA) but not the complement regulator factor H and did not decrease C3b deposition on the pneumococcal surface. PspK increased binding of pneumococci to epithelial cells and enhanced pneumococcal colonization independently of the genetic background. Understanding how NTSp colonizes and survives within the nasopharynx is important due to the increase in NTSp carriage. Our data suggest that PspK may aid in the persistence of NTSp within the nasopharynx but is not involved in invasion.
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Adhesión Bacteriana/inmunología , Proteínas Bacterianas/inmunología , Nasofaringe/microbiología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/inmunología , Animales , Antígenos de Superficie/inmunología , Antígenos de Superficie/metabolismo , Proteínas Bacterianas/metabolismo , Línea Celular , Complemento C3b/inmunología , Complemento C3b/metabolismo , Factor H de Complemento/inmunología , Factor H de Complemento/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Humanos , Inmunoglobulina A Secretora/inmunología , Inmunoglobulina A Secretora/metabolismo , Ratones , Ratones Endogámicos C57BL , Nasofaringe/inmunología , Infecciones Neumocócicas/metabolismo , Streptococcus pneumoniae/citología , Streptococcus pneumoniae/metabolismoRESUMEN
Prolonged inspiratory to expiratory (I:E) ratio ventilation may have both positive and negative effects on respiratory mechanics and oxygenation during one-lung ventilation (OLV), but definitive information is currently lacking. We therefore compared the effects of volume-controlled ventilation with I:E ratios of 1:1 and 1:2 on respiratory mechanics and oxygenation during OLV. Fifty-six patients undergoing thoracoscopic lobectomy were randomly assigned volume-controlled ventilation with an I:E ratio of 1:1 (group 1:1, n=28) or 1:2 (group 1:2, n=28) during OLV. Arterial and central venous blood gas analyses and respiratory variables were recorded 15 minutes into two-lung ventilation, at 30 and 60 minutes during OLV, and 15 minutes after two-lung ventilation was re-initiated. Peak and plateau airway pressures in cmH2O [standard deviation] during OLV were significantly lower in group 1:1 than in group 1:2 (P <0.01) (19 [3] and 23 [4]; 16 [3] and 19 [5], respectively). The arterial to end-tidal carbon dioxide tension difference was significantly lower in group 1:1 than in group 1:2 (P <0.01), (0.5 [0.3] and 1.1 [0.5]). There were no significant differences in PaO2 during OLV between the two groups (OLV30, P=0.856; OLV60, P=0.473). In summary, volume-controlled ventilation with an I:E ratio of 1:1 reduced peak and plateau airway pressures improved dynamic compliance and efficiency of alveolar ventilation, but it did not improve arterial oxygenation in a substantial manner. Furthermore, the associated increase in mean airway pressure might have reduced cardiac output, resulting in a lower central venous oxygen saturation.
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Consumo de Oxígeno , Postura , Respiración Artificial/métodos , Mecánica Respiratoria/fisiología , Adulto , Anciano , Análisis de los Gases de la Sangre , Dióxido de Carbono/metabolismo , Gasto Cardíaco , Femenino , Humanos , Masculino , Persona de Mediana Edad , Toracoscopía/métodos , Factores de TiempoRESUMEN
The relationship between temporomandibular joints (TMJ) osteoarthritis and masticatory muscle disorders is poorly understood. The data are sparse, the results are conflicting, and electromyographic (EMG) power spectrum analysis has not been used. The aims of this study were to compare the differences in EMG power spectrum during, and pressure pain thresholds (PPTs) before and after, sustained clenching in patients with unilateral TMJ osteoarthritis and healthy control subjects. Nineteen patients with unilateral TMJ osteoarthritis without masticatory muscle pain and 20 control subjects were evaluated. We measured EMG amplitudes at maximum voluntary contraction, median frequency from the EMG power spectrum during sustained clenching at 70% and PPTs before and after the clenching in both temporalis and masseter muscles. There were no significant differences in PPT decrease between muscles or between groups during sustained clenching. There were no significant differences in maximum voluntary contraction EMG activity ratios of affected to unaffected sides between groups, or of masseter to temporalis muscles between affected and unaffected side of patients with TMJ osteoarthritis. Median frequencies decreased from the beginning to the end of the sustained clench, and the interaction between group and clench was significant: the median frequency decrease was larger in the osteoarthritis group. Our results suggested that masticatory muscles of patients with unilateral TMJ osteoarthritis are more easily fatigued during sustained clenching than normal subjects.
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Músculo Masetero/fisiología , Fatiga Muscular/fisiología , Osteoartritis/fisiopatología , Músculo Temporal/fisiología , Síndrome de la Disfunción de Articulación Temporomandibular/fisiopatología , Adulto , Estudios de Casos y Controles , Estudios Transversales , Electromiografía/métodos , Femenino , Humanos , Masculino , Contracción Muscular/fisiología , Osteoartritis/diagnóstico por imagen , Dimensión del Dolor , Radiografía , Síndrome de la Disfunción de Articulación Temporomandibular/diagnóstico por imagenRESUMEN
BACKGROUND: We investigated the relationship between resumption or persistence of menstruation after cytotoxic chemotherapy (RM) and disease-free survival (DFS) in premenopausal patients with early breast cancer. METHODS: Medical records from 872 patients who received cytotoxic chemotherapy for stage I to III breast cancer were retrospectively reviewed. RESULTS: The median patient age was 41 years (range, 21-54) and the median follow-up duration was 6.2 years (range, 0.7-10.4). Six hundred ninety-two patients (79.4%) were hormone receptor (HR) positive and the majority of these received tamoxifen therapy after completing chemotherapy. The chemotherapy-induced amenorrhea (CIA) rate was 76.7% (n = 669), and 51.8% (n = 452) experienced RM during the follow-up period. One hundred twenty-one (13.9%) patients had persistent menstruation without CIA. DFS was significantly affected by younger age at diagnosis (≤35 years) (P = 0.013), tumor size > 2 cm (P < 0.001), node positivity (P < 0.001), HR negativity (P < 0.001), HER2 positivity (P = 0.010), and RM (P < 0.001). HR negativity [hazard ratio 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.006], tumor size > 2 cm (hazard ratio 2.1, 95% CI 1.4-3.0, P < 0.001), node positivity (hazard ratio 3.0, 95% CI 2.0-4.7, P < 0.001), and RM (hazard ratio 1.8, 95% CI 1.2-2.7, P = 0.004) remained significant factors for DFS on multivariate analysis. CONCLUSIONS: A considerable proportion of premenopausal patients treated with chemotherapy experienced RM after CIA. RM was a poor prognostic factor for DFS in premenopausal patients with early breast cancer.
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Amenorrea/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/fisiopatología , Ciclo Menstrual/efectos de los fármacos , Premenopausia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Capecitabina , Ciclofosfamida/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Metotrexato/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Taxoides/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Nasal polyposis is a multi-factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) accumulation are involved in the pathogenesis of nasal polyposis. OBJECTIVE: The aim of this study was to study the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on transforming growth factor (TGF)-ß1-induced myofibroblast differentiation and ECM accumulation in nasal polyp-derived fibroblasts (NPDFs). METHODS: Nasal polyp-derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA was treated in TGF-ß1-induced NPDFs. Expression levels of HDAC2, α-smooth muscle actin (SMA), TGF-ß1, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2/3 and Smad7 were determined by RT-PCR, western blot and/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC2 inhibition by TSA or HDAC2 silencing was established by RT-PCR and western blot. The epigenetic effect on α-SMA gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67-positive cell staining and cytotoxicity was assessed by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: The expression levels of HDAC2, α-SMA and TGF-ß1 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA and HDAC2 silencing inhibited expression levels α-SMA, collagen and HDAC2. TSA induced hyperacetylation of histone and suppressed opening of α-SMA gene promoter in TGF-ß1-induced NPDFs. TSA inhibited TGF-ß1-induced Smad 2/3 and rescued TGF-ß1-suppressed Smad7 signalling pathway. Finally, TSA blocked proliferation in TGF-ß1-induced NPDFs and has no cytotoxic effect in NPDFs. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that HDAC inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.
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Diferenciación Celular , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Miofibroblastos/citología , Miofibroblastos/metabolismo , Pólipos Nasales/genética , Pólipos Nasales/metabolismo , Acetilación/efectos de los fármacos , Actinas/genética , Actinas/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Epigénesis Genética , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Histona Desacetilasa 2/antagonistas & inhibidores , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Histonas/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Fosforilación/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Streptococcus pneumoniae expressing serogroup 6 capsules frequently causes pneumococcal infections and the evolutionary origins of the serogroup 6 strains have been extensively studied. However, these studies were performed when serogroup 6 had only two known members (serotypes 6A and 6B) and before the two new members (serotypes 6C and 6D) expressing wciN(ß) were found. We have therefore reinvestigated the evolutionary origins of serogroup 6 by examining the profiles of the capsule gene loci and the multilocus sequence types (MLSTs) of many serogroup 6 isolates from several continents. We confirmed that there are two classes of cps locus sequences for serogroup 6 isolates. In our study, class 2 cps sequences were limited to a few serotype 6B isolates. Neighbour-joining analysis of cps sequence profiles showed a distinct clade for 6C and moderately distinct clades for class 1 6A and 6B sequences. The serotype 6D cps profile was found within the class 1 6B clade, suggesting that it was created by recombination between 6C and 6B cps loci. Interestingly, all 6C isolates also had a unique wzy allele with a 6 bp deletion. This suggests that serotype switching to 6C involves the transfer of a large (>4 kb) gene segment that includes both the wciN(ß) allele and the 'short' wzy allele. The MLST studies of serotype 6C isolates suggest that the 6C cps locus is incorporated into many different pneumococcal genomic backgrounds but that, interestingly, 6C cps may have preferentially entered strains of the same genomic backgrounds as those of serotype 6A.
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Cápsulas Bacterianas/genética , Vías Biosintéticas/genética , Streptococcus pneumoniae/genética , Técnicas de Tipificación Bacteriana , Secuencia de Bases , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , Evolución Molecular , Orden Génico , Transferencia de Gen Horizontal , Sitios Genéticos , Genotipo , Humanos , Datos de Secuencia Molecular , Tipificación de Secuencias Multilocus , Filogenia , Recombinación Genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Serotipificación , Streptococcus pneumoniae/clasificaciónRESUMEN
OBJECTIVE: This study examined the neural pathophysiology of the theory of mind network by eliciting self-referential processing during an idea of reference evocating situation in patients with schizophrenia. METHOD: Functional MRI was conducted on 14 schizophrenic in-patients with the idea of reference and 15 healthy participants while viewing video vignettes of referential conversations, non-referential conversations or no conversations between two people, which were filmed at varying distances of 1, 5 or 10 m. RESULTS: The patient group did not show normal patterns of superior temporal sulcus activation to conversational context, and reciprocal deactivation and activation of the ventromedial and dorsomedial prefrontal cortex to referential conversational context. Instead, the patient group showed overall greater ventromedial prefrontal activities across different conversational contexts and inverse correlation between superior temporal sulcus activity and delusional severity. Differential activations of the temporal pole and its posterior extension to varying distances were observed in the control group but not in the patient group. CONCLUSION: The present study demonstrates that theory of mind-related responses of the medial prefrontal-superior temporal network are attenuated during the self-referential processing in patients with schizophrenia and that these abnormalities may be related to the formation of their referential or persecutory delusion.
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Imagen por Resonancia Magnética , Esquizofrenia/diagnóstico , Lóbulo Temporal/fisiopatología , Adulto , Mapeo Encefálico/métodos , Emociones/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Competencia Mental , Escalas de Valoración Psiquiátrica , Técnicas Psicológicas/instrumentación , Psicofisiología , Psicología del EsquizofrénicoRESUMEN
Among natural organic matter (NOM) defined as the complex matrix of organic materials abundant in natural waters, a gradual accumulation of recalcitrant organic matter (ROM) has been observed in impounded water bodies such as a lake or dam reservoir in spite of extensive efforts made to curtail organic pollutant loadings generated in their catchment areas. This paper aims to identify the effect of diffuse pollution resulting from allochthonous organic matters on the temporal and spatial characteristics of organic matters in a stratified dam reservoir, Daecheong Dam, using both intensive observation and CE-QUAL-W2 model simulation. With the limitation of observation data in terms of organic matters of inflow waters from boundary tributaries and impounded water in the reservoir, organic matter was represented by organic carbon including labile particular organic carbon (LPOC), refractory organic carbon (RPOC), labile dissolved organic carbon (LDOC), and refractory organic carbon (RDOC). Both autochthonous and allochthonous origins of organic carbon were considered in the modeling of eutrophication of the reservoir water using CE-QUAL-W2. The result of simulation during the period from 2001 to 2005 was observed to be a gradual accumulation of particular organic carbon (POC). It is clear that the model calculation results enable the explanation of the internal and external movement of constituents in the reservoir. In particular turbidity and NOM were well related in the upper region of the reservoir according to flow distance, gradually changing to dissolved form of organic matter, DOC affected organic matter concentration of reservoir water quality compared to turbidity.
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Oxígeno/química , Abastecimiento de Agua/análisis , Agua/química , Estudios de Evaluación como Asunto , Lluvia , República de Corea , Factores de Tiempo , Movimientos del Agua , Abastecimiento de Agua/normasRESUMEN
Optical data are essential for the accurate nondestructive determination of profiles of periodic structures in integrated-circuit technology. In rigorous coupled-wave analysis, the sample is generally modeled as layers consisting of a single material and the ambient. We extend present capabilities to the analysis of structures with overlayers and demonstrate our approach by determining quantitatively the thicknesses of top, sidewall, and bottom oxides of deliberately and naturally oxidized structures.
RESUMEN
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motoneuron disease. The etiology and precise pathogenic mechanisms of the disease remain unknown, and there is no effective treatment. Vascular endothelial growth factor (VEGF) has recently been shown to exert direct neurotrophic and neuroprotective effects in animal models of ALS. Here we show that intrathecal transplantation of immortalized human neural stem cells (NSCs) overexpressing human VEGF gene (HB1.F3.VEGF) significantly delayed disease onset and prolonged the survival of the SOD1G93A mouse model of ALS. At 4 weeks, post-transplantation grafted cells were found within the gray matter of the spinal cord. Furthermore, transplanted F3.VEGF cells that express neuronal phenotype (MAP2+) were found in the anterior horn of the spinal cord gray matter indicating that the transplanted human NSCs migrated into the gray matter, took the correct structural position, integrated into the spinal cord anterior horn and differentiated into motoneurons. Intrathecal transplantation of F3.VEGF cells provides a neuroprotective effect in the diseased spinal cord by concomitant downregulation of proapoptotic proteins and upregulation of antiapoptotic proteins. Our results suggest that this treatment modality of intrathecal transplantation of human NSCs genetically modified to overexpress neurotrophic factor(s) might be of value in the treatment of ALS patients without significant adverse effects.
Asunto(s)
Esclerosis Amiotrófica Lateral/terapia , Neuronas/trasplante , Trasplante de Células Madre/métodos , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Modelos Animales de Enfermedad , Supervivencia de Injerto , Humanos , Inyecciones Espinales , Ratones , Ratones Transgénicos , Microscopía Fluorescente , Actividad Motora/fisiología , Neuronas Motoras/metabolismo , Neuronas/metabolismo , Médula Espinal/metabolismo , Células Madre/metabolismo , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Recent studies have reported that glial cell line-derived growth factor (GDNF) has neurotrophic effects on the central nervous system, and the neural stem cells (NSCs) engrafted in animal models of stroke survive and ameliorate the neurological deficits. In this study, a stable human NSC line overexpressing GDNF (F3.GDNF) was transplanted next to the intracerebral hemorrhage (ICH) lesion site and a possible therapeutic effect was investigated. F3.GDNF human NSC line was transplanted into the cortex overlying the striatal ICH lesion. ICH was induced in adult mice by the unilateral injection of bacterial collagenase into the striatum. The animals were evaluated for 8 weeks with rotarod and limb placement tests. Transplanted NSCs were detected by beta-gal immunostaining with double labeling of neurofilament, microtubule associated protein-2, glial fibrillary acidic protein or human nuclear matrix antigen (HuNuMA). F3.GDNF human NSCs produced a four times higher amount of GDNF over parental F3 cells in vitro, induced behavioral improvement in ICH mice after brain transplantation and two- to threefold increase in cell survival of transplanted NSCs at 2 and 8 weeks post-transplantation. In F3.GDNF-grafted ICH brain, a significant increase in the antiapoptotic protein and cell survival signal molecules, and a marked reduction in proapoptotic proteins were found as compared with control group. Brain transplantation of human NSCs overexpressing GDNF in ICH animals provided functional recovery in ICH animals, and survival and differentiation of grafted human NSCs. These results indicate that the F3.GDNF human NSCs should be of a great value as a cellular source for the cellular therapy in animal models of human neurological disorders including ICH.
Asunto(s)
Hemorragia Cerebral/terapia , Terapia Genética/métodos , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Neuronas/trasplante , Trasplante de Células Madre/métodos , Animales , Apoptosis , Trasplante de Tejido Encefálico/métodos , Diferenciación Celular , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/fisiopatología , Vectores Genéticos , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Supervivencia de Injerto , Humanos , Ratones , Ratones Endogámicos ICR , Neuronas/metabolismo , Recuperación de la Función , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
This paper describes MEMS micromirror characterization in space environments associated with our space applications in earth observation from the International Space Station and earth's orbit satellite. The performance of the micromirror was tested for shock and vibration, stiction, outgassing from depressurization and heating, and electrostatic charging effects. We demonstrated that there is no degradation of the micromirror performance after the space environment tests. A test bed instrument equipped with the micromirrors was delivered and tested in the ISS. The results demonstrate that the proposed micromirrors are suitable for optical space systems.