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The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (â¼93∘ inclination), nearly circular, low-Earth (â¼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit â¼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a â¼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin â¼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.
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BACKGROUND: Endoscopic ultrasonography (EUS) and narrow band imaging-magnifying endoscopy (NBI-ME) are often used as diagnostic tools to estimate the depth of invasion in early colorectal cancer (CRC). The aim of this study was to compare NBI-ME with EUS in distinguishing between slight submucosal invasion (invasion depth < 1000 µm) and massive submucosal invasion in patients with early CRC, since slight submucosal invasion is currently considered as an indication for endoscopic resection. METHODS: For this meta-analysis, relevant studies were identified from PubMed, Embase, Web of Science, Scopus and the Cochrane Library databases between January 1997 and September 2016. Data on the yield of tumors were extracted, pooled, and analyzed by stata12.0 software. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio in differentiating slight submucosal invasion from massive submucosal invasion were calculated for both diagnostic modalities. RESULTS: Sixteen studies involving 2197 lesions were included: nine were studies on EUS and 7 were studies on NBI-ME. The pooled sensitivity of EUS was 0.902 (95% CI 0.863-0.930), the specificity was 0.877 (95% CI 0.810-0.922), the positive likelihood ratio was 7.314 (95% CI 4.551-11.755) and the negative likelihood ratio was 0.112 (95% CI 0.076-0.164). The pooled sensitivity and specificity of NBI-ME were 0.981 (95% CI 0.949-0.993) and 0.651 (95% CI 0.600-0.699), respectively, the positive likelihood ratio was 2.815 (95% CI 2.432-3.258) and the negative likelihood ratio was 0.029 (95% CI 0.010-0.080). CONCLUSIONS: The sensitivity tended to be higher in ME-NBI than EUS for early CRC with slight submucosal invasion, whereas the specificity was significantly lower in NBI-ME than in EUS.
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Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Endosonografía , Imagen de Banda Estrecha , Humanos , Invasividad Neoplásica , Sensibilidad y EspecificidadRESUMEN
Objective To investigate the structure and biomechanical property differences in different regions of the femoral head for elderly patients with femoral neck fractures, and to study its influence on internal fixation for fracture. Methods Twenty femoral head specimens were collected from elderly patients with femoral neck fracture after joint replacement. The femoral head was divided into 3 parts (lateral, inferior and medial region) with reference to anatomical markers on surface of the femoral head. After the position and drilling direction of the ring drill were determined, a circular drill was used to obtain the cylindrical cancellous bone columns with 10 mm in diameter and 10 mm in height. The data of cancellous bone columns in different regions were analyzed by Micro-CT scanning system, including bone volume fraction (BVF), trabecular space (Tb.Sp), trabecular thickness (Tb.Th), the number of trabecular number (Tb.N), the bone surface volume ratio (bone surface/bone volume, BS/BV), structural model index (SMI). Mechanical property differences of bone tissues in different regions were calculated by micro-finite element analysis. ResultsBone mass in the elderly osteoporotic femoral head decreased, and there were significant differences in bone microstructure and mechanical properties in different regions of the femoral head. Bone microstructure and mechanical properties in medial region were obviously superior to those in lateral and interior region. Conclusions The bone structure and mechanical strength in medial region of the femoral head are obvious superior to those in lateral and inferior regions. The position for internal fixation should be fully considered during treatment of osteoporotic femoral neck fracture in clinic.
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BACKGROUND: This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC). METHODS: Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m(-2), folinic acid 400 mg m(-2), and 5-fluorouracil (400 mg m(-2) bolus then 2400 mg m(-2) over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate. RESULTS: Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0-16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0-30.0) and 10.0 months (7.0-12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0-NA); median PFS 12.0 (8.0-20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0-37.0); median PFS 7.0 (4.0-18.0)). The most common grade ⩾3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%). CONCLUSION: First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Proteínas Proto-Oncogénicas p21(ras)/genética , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The 40 Mb T1D susceptibility locus Iddm26 was mapped to chromosome 2 through linkage analysis of a conditioned cross-intercross between the diabetes-prone BBDP and the diabetes-resistant ACI.BBDP-Iddm1,Iddm2 (ACI.1u.Lyp). It is flanked by Iddm32 and Iddm33, which control the kinetics of disease progression. To fine-map Iddm26 and characterize immune phenotypes controlled by this locus, several congenic sublines were generated carrying smaller, overlapping intervals spanning Iddm26 and fragments of Iddm32 and 33. Analysis of disease susceptibility, age of disease onset, and immune phenotypes in these sublines identified subloci regulating these different parameters. Two ACI.1u.Lyp-derived subloci, Iddm26.1 and Iddm26.2, imparted significant protection from diabetes, decreasing the cumulative incidence by as much as 57% and 28%, respectively. Iddm26.2, which overlaps with the human PTPN22 locus, only affected disease susceptibility, whereas Iddm26.1 also significantly affected disease kinetics, delaying T1D onset by more than 10 days compared with the parental BBDP strain. These Iddm26 subloci also regulated various immune phenotypes, including the proportion of splenic macrophages by Iddm26.1, and the proportion of activated T-cells in secondary lymphoid organs by Iddm26.2. The analysis of Iddm26 congenic animals in two different SPF facilities demonstrated that the influence of this locus on T1D is environment-dependent.
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Mapeo Cromosómico/métodos , Cromosomas de los Mamíferos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Animales , Cruzamientos Genéticos , Diabetes Mellitus Tipo 1/sangre , Femenino , Ligamiento Genético , Sitios Genéticos/genética , Sitios Genéticos/inmunología , Predisposición Genética a la Enfermedad/genética , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas BB , Organismos Libres de Patógenos Específicos , Bazo/inmunología , Bazo/metabolismo , Análisis de Supervivencia , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Timocitos/citología , Timocitos/inmunología , Timocitos/metabolismoRESUMEN
Extracellular matrix (ECM) in chondrocytes-seeded agarose aggregates to form islands of matrix. These islands need to coalesce to develop functional cartilage. Hence, macroscopic properties are determined by transport and aggregation of macromolecules at the microscale, which varies temporally and spatially. This study evaluates the importance of the mutual interaction between matrix components and matrix development. Fluorescence recovery after photobleaching measurements demonstrates that diffusivity depends on the presence and density of ECM. A reaction-diffusion model describing synthesis, transport and immobilisation of ECM predicts steep gradients in ECM around chondrocytes, resembling histology. Steric hindrance of diffusion by ECM is essential for the formation of these gradients. Finally, microscopic ECM concentration is linked with macroscopic mechanical properties. Construct softening is predicted when temporal and spatial variations in diffusivity are considered. In conclusion, non-constant diffusion renders significant effects on both the microscopic ECM development and the macroscopic mechanical properties of developing tissue-engineered cartilage.
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Cartílago/fisiología , Modelos Biológicos , Ingeniería de Tejidos , Animales , Fenómenos Biomecánicos , Células Cultivadas , Condrocitos/fisiología , Simulación por Computador , Matriz Extracelular/fisiología , Recuperación de Fluorescencia tras Fotoblanqueo , Geles , Glicosaminoglicanos/metabolismo , Sefarosa , Porcinos , Soporte de Peso/fisiologíaRESUMEN
INTRODUCTION: Endometrial carcinoma is the one of the leading causes of terminal cancer death in women, and the best way to solve it is through an early diagnosis. Serum proteomic profiling is a promising approach to classify disease versus normal and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). This analysis is a new potential tool for the diagnosis of human diseases. The objective of our study was to assess the feasibility of mass spectrometry, based on serum proteomic pattern for the discrimination of endometrial carcinoma patients from healthy control patients. MATERIAL AND METHODS: By using 30 pre-operative endometrial carcinoma serum samples and 30 healthy controls, we generated MALDI-TOF protein profiles, established the serum detection model, and analyzed the data. Furthermore, we validated the data and got the total sensitivity (97.6%) and specificity (100%), which could classify all the samples well and demonstrated the high, significant separation ability. RESULTS: Our results indicated that high sensitivity and specificity classify endometrial carcinoma by the serum detection model and showed the potential usefulness of serum protein profiles. CONCLUSIONS: From these results, we could tell that MALDI-TOF MS is a potential tool for diagnosing diseases by the use of serum samples and will be widely used in the future for clinical work.
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The classical theory of wave propagation in elastic cylinders is extended to poro-elastic mandrel modes. The classical theory predicts the existence of undamped L modes and damped C, I, and Z modes. These waves also appear in poro-elastic mandrels, but all of them become damped because of viscous effects. The presence of the Biot slow bulk wave in the poro-elastic material is responsible for the generation of additional mandrel modes. One of them was already discussed by Feng and Johnson, and the others can be grouped together as so-called D modes. The damping of these D modes is at least as high as the damping of the free-field slow wave.
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In this paper guided wave modes in porous media are investigated. A water-saturated porous cylinder is mounted in the test section of a shock tube. Between the porous sample and the wall of the shock tube a water-filled annulus exists. For very small annulus width, bulk waves are generated and one-dimensional modeling is sufficient. Otherwise two-dimensional effects become important and multiple guided wave modes occur. Using a newly developed traversable positioning system in the shock tube, the frequency-dependent phase velocities and damping coefficients in the 1-120 kHz frequency range were measured. Prony's method was used for data processing. Agreement was found between the experimental data and the two-dimensional modeling of the shock tube which was based on Biot's theory.
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Five kinds of ear mushrooms are commercially available in Taiwan, including black, red, jin, snow, and silver ears. Methanolic extracts were prepared from these ear mushrooms, and their antioxidant properties were studied. For all methanolic extracts from ear mushrooms, the antioxidant activities in the 1,3-diethyl-2-thiobarbituric acid method were moderate (38.6 approximately 74.6%) at 1.0-5.0 mg/mL. Methanolic extracts from red, jin, and snow ears showed excellent antioxidant activities in the conjugated diene method at 5.0 mg/mL. At 5.0 mg/mL, reducing powers of methanolic extracts were in the descending order of snow > black approximately red approximately jin > silver ears. The scavenging effect of methanolic extracts from ear mushrooms on 1,1-diphenyl-2-picrylhydrazyl radicals was excellent except for that from silver ears. Ear mushroom extracts were not good scavengers for hydroxyl free radicals but were good chelators for ferrous ions. Naturally occurring antioxidants, including ascorbic acid, tocopherols, and total phenols, were found in the methanolic extracts. However, beta-carotene was not detected. Total antioxidant components were 15.69, 30.09, 27.83, 49.17, and 31.70 mg/g for black, red, jin, snow, and silver ears, respectively.
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Agaricales/química , Antioxidantes/química , Bepridil/análogos & derivados , Picratos , Bepridil/química , Compuestos de Bifenilo , Depuradores de Radicales Libres/química , Radical Hidroxilo/química , Metanol/química , Oxidación-ReducciónRESUMEN
OBJECTIVE: To compare the survival between intraperitoneal cisplatin-based chemotherapy (IPCT) and intravenous cisplatin-based chemotherapy (IVCT) in stage III epithelial ovarian cancer with minimal residual disease (<1 cm) after primary debulking surgery. METHOD: One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a randomized clinical trial in which IPCT or IVCT was administered at 3-week intervals. Patients in the IPCT arm received cisplatin-based (100 mg/m(2)) intraperitoneal chemotherapy. Patients in the IVCT arm received cisplatin-based (50 mg/m(2)) intravenous chemotherapy. The tumor response was assessed every 3 months. The hematological toxicity using the South West Oncology Group (SWOG) toxicity criteria was assessed. Catheter complications associated with intraperitoneal chemotherapy were also analyzed. RESULT: The estimated median survival in the IPCT group was 43 months (95% confidence interval, 34-54) and IVCT group was 48 months (95% confidence interval, 37-59). The hazard ratio of death was not statistically significant between IPCT and IVCT (hazard ratio, 1.13; 95% CI, 0.69-1.86; P=0.317). The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group. CONCLUSION: Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/cirugía , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Intraperitoneales , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Ovariectomía/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Hyperamylasemia and alternations of serum isoamylases have been recorded in lung tumors, tubal disorders such as acute salpingitis and ruptured ectopic pregnancies and a variety of ovarian tumors, and they have been suggested as potential tumor markers. Hyperamylasemia was noted in a patient with a stage IIIC endometroid adenocarcinoma of the ovary. Serum levels of amylase decreased rapidly after removal of the ovarian tumor. In patients presenting with acute abdominal pain and elevated amylase levels, ovarian cancer should be considered in addition to acute pancreatitis.
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Amilasas/sangre , Carcinoma Endometrioide/enzimología , Neoplasias Ováricas/enzimología , Dolor Abdominal/etiología , Adulto , Femenino , HumanosRESUMEN
We report the cloning of the gene encoding the 32-kDa lipoprotein, designated LipL32, the most prominent protein in the leptospiral protein profile. We obtained the N-terminal amino acid sequence of a staphylococcal V8 proteolytic-digest fragment to design an oligonucleotide probe. A Lambda-Zap II library containing EcoRI fragments of Leptospira kirschneri DNA was screened, and a 5.0-kb DNA fragment which contained the entire structural lipL32 gene was identified. Several lines of evidence indicate that LipL32 is lipid modified in a manner similar to that of other procaryotic lipoproteins. The deduced amino acid sequence of LipL32 would encode a 272-amino-acid polypeptide with a 19-amino-acid signal peptide, followed by a lipoprotein signal peptidase cleavage site. LipL32 is intrinsically labeled during incubation of L. kirschneri in media containing [(3)H]palmitate. The linkage of palmitate and the amino-terminal cysteine of LipL32 is acid labile. LipL32 is completely solubilized by Triton X-114 extraction of L. kirschneri; phase separation results in partitioning of LipL32 exclusively into the hydrophobic, detergent phase, indicating that it is a component of the leptospiral outer membrane. CaCl(2) (20 mM) must be present during phase separation for recovery of LipL32. LipL32 is expressed not only during cultivation but also during mammalian infection. Immunohistochemistry demonstrated intense LipL32 reactivity with L. kirschneri infecting proximal tubules of hamster kidneys. LipL32 is also a prominent immunogen during human leptospirosis. The sequence and expression of LipL32 is highly conserved among pathogenic Leptospira species. These findings indicate that LipL32 may be important in the pathogenesis, diagnosis, and prevention of leptospirosis.
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Leptospira/genética , Leptospira/inmunología , Lipoproteínas/inmunología , Lipoproteínas/metabolismo , Acilación , Secuencia de Aminoácidos , Animales , Proteínas de la Membrana Bacteriana Externa/inmunología , Secuencia de Bases , Southern Blotting , Clonación Molecular , Cricetinae , Detergentes/farmacología , Ensayo de Inmunoadsorción Enzimática , Escherichia coli/metabolismo , Ácidos Grasos/metabolismo , Immunoblotting , Infecciones , Riñón/microbiología , Riñón/patología , Leptospirosis/sangre , Lipoproteínas/genética , Mesocricetus , Datos de Secuencia Molecular , Octoxinol , Filogenia , Polietilenglicoles/farmacología , Pruebas de Precipitina , Factores de TiempoRESUMEN
New vaccine strategies are needed for prevention of leptospirosis, a widespread human and veterinary disease caused by invasive spirochetes belonging to the genus Leptospira. We have examined the immunoprotective capacity of the leptospiral porin OmpL1 and the leptospiral outer membrane lipoprotein LipL41 in the Golden Syrian hamster model of leptospirosis. Specialized expression plasmids were developed to facilitate expression of leptospiral proteins in Escherichia coli as the membrane-associated proteins OmpL1-M and LipL41-M. Although OmpL1-M expression is highly toxic in E. coli, this was accomplished by using plasmid pMMB66-OmpL1, which has undetectable background expression without induction. LipL41-M expression and processing were enhanced by altering its lipoprotein signal peptidase cleavage site to mimic that of the murein lipoprotein. Active immunization of hamsters with E. coli membrane fractions containing a combination of OmpL1-M and LipL41-M was found to provide significant protection against homologous challenge with Leptospira kirschneri serovar grippotyphosa. At 28 days after intraperitoneal inoculation, survival in animals vaccinated with both proteins was 71% (95% confidence interval [CI], 53 to 89%), compared with only 25% (95% CI, 8 to 42%) in the control group (P < 0.001). On the basis of serological, histological, and microbiological assays, no evidence of infection was found in the vaccinated survivors. The protective effects of immunization with OmpL1-M and LipL41-M were synergistic, since significant levels of protection were not observed in animals immunized with either OmpL1-M or LipL41-M alone. In contrast to immunization with the membrane-associated forms of leptospiral proteins, hamsters immunized with His(6)-OmpL1 and His(6)-LipL41 fusion proteins, either alone or in combination, were not protected. These data indicate that the manner in which OmpL1 and LipL41 associates with membranes is an important determinant of immunoprotection.
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Proteínas de la Membrana Bacteriana Externa/inmunología , Inmunización , Leptospira/inmunología , Leptospirosis/prevención & control , Animales , Anticuerpos Antibacterianos/sangre , Proteínas de la Membrana Bacteriana Externa/genética , Cricetinae , Modelos Animales de Enfermedad , Leptospira/genética , Leptospira/metabolismo , Leptospirosis/inmunología , Leptospirosis/mortalidad , Dosificación Letal Mediana , Mesocricetus , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes/inmunologíaRESUMEN
Congenital ptosis in humans has been associated with anisometropia, myopia, astigmatism, and amblyopia. Scientific evidence has shown that visual deprivation causes axial myopia in animals. This study using chicks was undertaken to investigate an animal model of congenital ptosis and the effects of lid position on ocular development. Eyelid ptosis was surgically induced in one eye each of white leghorn chickens within 48 hours after hatching. The chicks were raised under natural diurnal lighting. Thirty days after inducing ptosis, the chicks were killed and their eyes enucleated and photographed in a sagittal view. Computerized image analysis was used to measure the size of the globe along five axes. Globe size was significantly greater in the superior part of eyes with ptosis compared with control eyes. No other measurement differences were significant (p < 0.01). Thus, this study demonstrates that regional axial myopia is induced by eyelid ptosis in chicks.
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Blefaroptosis/congénito , Modelos Animales de Enfermedad , Ojo/patología , Miopía/etiología , Animales , Blefaroptosis/complicaciones , Pollos , Ojo/crecimiento & desarrollo , Estudios de Seguimiento , Procesamiento de Imagen Asistido por Computador , Miopía/patología , Distribución AleatoriaRESUMEN
The sucABCD genes of Escherichia coli encode subunits for two enzymes of the tricarboxylic acid (TCA) cycle, alpha-ketoglutarate dehydrogenase (sucAB) and succinyl coenzyme A synthetase (sucCD). To examine how these genes are expressed in response to changes in oxygen and carbon availability, a set of sucA-lacZ, sucC-lacZ, sdhCDAB-sucA-lacZ, and sdhC-lacZ fusions were constructed and analyzed in vivo. While the expression of a sucA-lacZ fusion was low under all cell growth conditions tested, the expression of the sucA gene from the upstream sdhC promoter was considerably higher and varied by up to 14-fold depending on the carbon substrate used. Expression of the sdhCDAB-sucA-lacZ fusion varied by fourfold in response to oxygen. In contrast, no expression was seen from a sucC-lacZ reporter fusion, indicating that no promoter immediately precedes the sucCD genes. Taken together, these findings demonstrate that the oxygen and carbon control of sucABCD gene expression occurs by transcriptional regulation of the upstream sdhC promoter. The weaker sucA promoter provides an additional low constitutive level of sucABCD gene expression to supplement transcription from the sdhC promoter. The negative control of sucABCD gene expression seen under anaerobic conditions, like that for the sdhCDAB genes, is provided by the arcA and fnr gene products. These findings establish that the differential expression of eight genes for three of the TCA cycle enzymes in E. coli is controlled from one regulatory element.
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Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Proteínas de Escherichia coli , Escherichia coli/enzimología , Regulación Bacteriana de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Proteínas Hierro-Azufre/genética , Complejo Cetoglutarato Deshidrogenasa/genética , Regiones Promotoras Genéticas , Proteínas Represoras , Succinato Deshidrogenasa/genética , Succinato-CoA Ligasas/genética , Aerobiosis , Carbono , Proteínas Portadoras/genética , Escherichia coli/genética , Genes Reporteros , Factores de Integración del Huésped , Hierro/metabolismo , Operón Lac , Oxígeno , Proteínas Recombinantes de Fusión/genética , Transcripción GenéticaRESUMEN
Isocitrate dehydrogenase, the icd gene product, has been studied extensively regarding the regulation of enzymatic activity and its relationship to the metabolic flux between the tricarboxylic acid cycle and the glyoxylate bypass. In this study, the transcriptional regulation of icd gene expression was monitored by using an icd-lacZ gene fusion and shown to vary over a 15-fold range in response to changes in oxygen and carbon availability. Anaerobic cell growth resulted in fivefold-lower icd-lacZ expression than during aerobic growth. This negative control is mediated by the arcA and fnr gene products. When different carbon compounds were used for cell growth, icd-lacZ expression varied threefold. The results of continuous cell culture studies indicated that this control may be due to variations in cell growth rate rather than to catabolite repression. DNase I footprinting at the icd promoter revealed a 42-bp ArcA-phosphate-protected region that overlaps the start site of icd transcription. Phosphorylation of ArcA considerably enhanced its binding to DNA, while ArcA-phosphate exhibited an apparent dissociation value of approximately 0.1 microM. Based on these studies, ArcA appears to function as a classical repressor of transcription by binding at a site overlapping the icd promoter during anaerobic cell growth conditions.
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Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Proteínas de Escherichia coli , Escherichia coli/enzimología , Regulación Bacteriana de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Proteínas Hierro-Azufre/genética , Isocitrato Deshidrogenasa/genética , Oxígeno , Proteínas Represoras , Acetatos/farmacología , Aerobiosis , Secuencia de Bases , Sitios de Unión , División Celular , Medios de Cultivo , ADN Bacteriano , Escherichia coli/crecimiento & desarrollo , Glucosa/farmacología , Operón Lac , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , ARN Mensajero , Proteínas Recombinantes de Fusión/genéticaRESUMEN
Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that play critical roles in the detoxification of xenobiotics and the protection of tissues against oxidative damage. GSTs are important enzymes in plant responses to a number of environmental stresses including herbicides and pathogen attack. Ocs elements are a group of related, 20 bp promoter elements which have been exploited by some plant pathogens to express genes in plants. Ocs elements have also been found to regulate the expression of a plant GST promoter. An Arabidopsis GST gene, called GST6 has been isolated. GST6 expression is under tissue-specific control and is induced following treatment with auxin, salicylic acid and H2O2. The GST6 promoter contains a binding site for two Arabidopsis ocs element binding factors (OBF), that has some sequence homology to ocs element sequences. Interestingly, OBP1 (OBF binding protein), a DNA-binding protein that was isolated by screening an Arabidopsis cDNA library with a labeled OBF protein as a probe, binds next to the OBF-binding site on the GST6 promoter. OBP1 was able to significantly stimulate the binding of OBF proteins to the GST6 promoter, raising the possibility that interactions between the OBP1 and OBF proteins may be important for GST6 expression.
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Arabidopsis/genética , Regulación Enzimológica de la Expresión Génica , Glutatión Transferasa/genética , Peróxido de Hidrógeno/farmacología , Regiones Promotoras Genéticas , Secuencia de Aminoácidos , Arabidopsis/enzimología , Secuencia de Bases , Sitios de Unión , Proteínas de Unión al ADN/metabolismo , Dosificación de Gen , Genes de Plantas , Glutatión Transferasa/biosíntesis , Ácidos Indolacéticos/farmacología , Datos de Secuencia Molecular , Proteínas de Plantas/metabolismo , ARN Mensajero/biosíntesis , ARN de Planta/biosíntesis , Salicilatos/farmacología , Ácido Salicílico , Homología de Secuencia de Aminoácido , Transcripción GenéticaRESUMEN
OBJECTIVE: To determine if there are histopathologic changes in the outer retina that could explain the blue-yellow color confusion previously described following rhegmatogenous retinal detachment in humans. METHODS: Ten eyes with traumatic retinal detachments were studied. Eight of the eyes were removed from 2 1/2 to 11 days following trauma. In the remaining two eyes, the retinas were successfully reattached. Enzyme histochemical studies for carbonic anhydrase and immunochemical studies for S antigen were performed to distinguish blue cones from red/green cones. RESULTS: With the 2 1/2- to 4-day-old detachments, nearly all of the carbonic anhydrase-negative (blue-sensitive) cones and many of the rods were seen to have signs of irreversible necrosis, including extreme swelling of the inner segments and mitochondria, loss of the outer segments, and pyknotic and displaced nuclei. In the 6- and 11-day-old detachments, almost all of the carbonic anhydrase-negative cones and many rods were missing. Blue cones were essentially absent from the reattached retinas, and there were only about half the normal number of rods. CONCLUSIONS: Rhegmatogenous retinal detachment results in rapid and almost total loss of the blue cones. Significant rod loss also occurs in this type of detachment but the red/green cones are comparatively resistant to damage. These findings could explain the observed blue-yellow color confusion in such patients. We discuss other clinical implications.
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Defectos de la Visión Cromática/etiología , Lesiones Oculares/complicaciones , Células Fotorreceptoras/patología , Retina/lesiones , Desprendimiento de Retina/etiología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Antígenos/metabolismo , Arrestina , Anhidrasas Carbónicas/metabolismo , Defectos de la Visión Cromática/patología , Enucleación del Ojo , Proteínas del Ojo/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Necrosis , Células Fotorreceptoras/metabolismo , Desprendimiento de Retina/patologíaRESUMEN
We determined subjects' responses to sine-wave modulated lights employing visually evoked potentials (VEPs) and psychophysical thresholds in a series of experiments. The stimuli had the same temporal frequency and mean luminance in each eye but the phase difference between the two eyes was varied so that phase was either the same (dioptic) or different (dichoptic) in the two eyes. The data were fit by a model which had two binocular pathways, one which summed monocular nonlinear elements and a second which had a nonlinearity following the combination of monocular linear elements. In the second channel the outputs of the monocular linear elements were summed at low luminance while at higher luminance levels they were subtracted. Based on variations in the threshold data with temporal frequency, the pathway which summed nonlinear monocular elements was identified with the magnocellular (M) pathway, and the pathway which combined monocular linear elements prior to a binocular nonlinear element was identified with the parvocellular (P) pathway.