RESUMEN
Metasurfaces are a new class of diffractive optical elements with subwavelength elements whose behavior can be lithographically tailored. By leveraging form birefringence, metasurfaces can serve as multifunctional freespace polarization optics. Metasurface gratings are novel, to the best of our knowledge, polarimetric components that integrate multiple polarization analyzers into a single optical element enabling the realization of compact imaging polarimeters. The promise of metasurfaces as a new polarization building block is contingent on the calibration of metagrating-based optical systems. A prototype metasurface full Stokes imaging polarimeter is compared to a benchtop reference instrument using an established linear Stokes test for 670, 532, and 460 nm gratings. We propose a complementary full Stokes accuracy test and demonstrate it using the 532 nm grating. This work presents methods and practical considerations involved in producing accurate polarization data from a metasurface-based Stokes imaging polarimeter and informs their use in polarimetric systems more generally.
RESUMEN
BACKGROUND: The COVID-19 pandemic has severely impacted the learning experience of students by limiting their opportunities for face-to-face intercultural exchanges. Given the importance of cultural competence in medical education, there is a need to develop a programme that promotes cultural awareness, but that offers more flexibility in terms of outbound mobility. This study aims to evaluate the effectiveness of an internationalization at home programme and to explore the learning experiences of medical and nursing students from Hong Kong and Indonesia. METHODS: Students were recruited from two universities in Hong Kong and Indonesia. They attended an online internationalization at home programme designed by members of the research team from both countries. A mixed-methods study was conducted using a concurrent triangulation approach. A pre-test post-test design was used to evaluate the effects of the programme on cultural awareness, and four focus groups were conducted to explore the students' experiences in the programme. Quantitative and qualitative data were analysed by T-test and reflexive thematic analysis, respectively. Data were integrated and triangulated using joint displays by comparing findings from both sources. RESULTS: One hundred and forty-eight students from Hong Kong and Indonesia participated in the study. After the programme, there was a significant improvement in cultural awareness. Three themes were identified: (1) learning process: enjoyable, but a desire remains for face-to-face cross-cultural communication; (2) learning outcomes: gained cultural awareness, developed cultural sensitivity, had an opportunity to practice language and learn about new learning styles; (3) factors influencing learning outcomes: facilitators (micro-movie and active communication) and barriers (language barrier, inappropriate time arrangement, insufficient prior briefing). CONCLUSION: This programme achieved the learning outcomes by successfully enhancing the cultural awareness of students during a time of pandemic when outbound student exchanges were not possible. Further adaptations of the programme are required to enhance different learning outcomes.
Asunto(s)
COVID-19 , Estudiantes de Enfermería , COVID-19/epidemiología , Competencia Cultural/educación , Hong Kong , Humanos , Indonesia , Pandemias , Investigación CualitativaRESUMEN
In light of the present pandemic of novel coronavirus disease 2019 (COVID-19) and the unprecedented high demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing worldwide, there are shortages of established specimen collection devices for respiratory viral testing for diagnostic microbiology laboratories. This creates the need to validate unverified collection devices from manufacturers that may not be a registered supplier for medical devices. As clinical laboratories do not routinely perform quality control of established collection devices, there is a need to have a systematic, robust approach to the assessment of substitute unregistered collection swabs and viral transport media (VTM). A discussion of the aspects requiring consideration when determining the suitability and implementation of new collection devices is presented. These specific assessment criteria include an inspection of device integrity, determination of swab and VTM sterility and in vitro performance, VTM stability, and examination of the clinical performance of the device. This method was used in a front-line medical microbiology laboratory on swabs and VTM from an unregistered manufacturer, with suboptimal results that precluded implementation. As the pandemic continues, it will be important for diagnostic laboratories to adopt a flexible and streamlined approach to maintaining adequate supply chains for testing reagents and materials.
Asunto(s)
Prueba de COVID-19/instrumentación , COVID-19/diagnóstico , Manejo de Especímenes/instrumentación , Técnicas de Laboratorio Clínico , Humanos , Pandemias , SARS-CoV-2RESUMEN
Mueller polarized bi-directional scattering distribution functions (pBSDFs) are 4 × 4 matrix-valued functions which depend on acquisition geometry. A widely used backscattering pBSDF model proposed by Priest and Meier [Opt. Eng.41, 988 (2002)10.1117/1.1467360] is a weighted sum between a Fresnel matrix and an ideal depolarizer. This work's main contribution is relating the relative weight between an ideal depolarizer and Fresnel matrix to a single depolarization parameter. Rather than a 16-dimensional matrix norm, this parameter can form a one-dimensional merit function. Then, instead of a full Mueller matrix measurement, a scheme for pBSDF fitting to only two polarimetric measurements is introduced. Depolarization can be mathematically expressed as the incoherent addition of coherent states [J. Opt. Soc. Am. A30, 691 (2013)10.1364/JOSAA.30.000691]. This work shows that, for a Mueller matrix to be in the span of a Fresnel matrix and an ideal depolarizer, the weights in the incoherent addition are triply degenerate. This triple degeneracy is observed in five different colored opaque plastics treated with nine different surface textures and measured at varying acquisition geometries and wavebands.
RESUMEN
An imaging Mueller matrix polarimeter, named the red-green-blue (RGB)950, takes images of medium-sized (tens of centimeters) objects by using a very bright source, large polarization state generator, and high-quality camera. Its broadband extended light source switches between red, green, blue, and near-infrared light to allow taking polarimetric images for comparison with RGB camera images. The large diffuse source makes shadow transitions gradual and spreads out the specular reflected spot into a larger less conspicuous area.
RESUMEN
High-entropy alloy (HEA) offers great flexibility in materials design with 3-5 principal elements and a range of unique advantages such as good microstructure stability, mechanical strength over a broad range of temperatures and corrosion resistance, etc. Welding of high entropy alloy, as a key joining method, is an important emerging area with significant potential impact to future application-oriented research and technological developments in HEAs. The selection of feasible welding processes with optimized parameters is essential to enhance the applications of HEAs. However, the structure of the welded joints varies with material systems, welding methods and parameters. A systemic understanding of the structures and properties of the weldment is directly relevant to the application of HEAs as well as managing the effect of welding on situations such as corrosion that are known to be a service life limiting factor of welded structures in conditions such as marine environments. In this paper, key recent work on welding of HEAs is reviewed in detail focusing on the research of main HEA systems when applying different welding techniques. The experimental details including sample preparation, sample size (thickness) and welding conditions reflecting energy input are summarized and key issues are highlighted. The microstructures and properties of different welding zones, in particular the fusion zone (FZ) and the heat affected zones (HAZ), formed with different welding methods are compared and presented in details and the structure-property relationships are discussed. The work shows that the weldability of HEAs varies with the HEA composition groups and the welding method employed. Arc and laser welding of AlCoCrFeNi HEAs results in lower hardness in the FZ and HAZ and reduced overall strength. Friction stir welding results in higher hardness in the FZ and achieves comparable/higher strength of the welded joints in tensile tests. The welded HEAs are capable of maintaining a reasonable proportion of the ductility. The key structure changes including element distribution, the volume fraction of face centered cubic (FCC) and body centered cubic (BCC) phase as well as reported changes in the lattice constants are summarized and analyzed. Detailed mechanisms governing the mechanical properties including the grain size-property/hardness relationship in the form of Hall-Petch (H-P) effect for both bulk and welded structure of HEAs are compared. Finally, future challenges and main areas to research are highlighted.
RESUMEN
Early and rapid detection of patients with HIV is a key to preventing further transmission. The purpose of this study was to assess the ability of signal-to-cutoff (S/CO) ratio from initial screening fourth-generation HIV serology to predict subsequent confirmation of HIV. Patients with a first-time positive HIV serology (S/CO ratio ≥ 1) from 2012 to 2016 were included. Ratios were compared to the results of confirmatory testing. Predictive probabilities (PPs) of a positive confirmatory result were calculated based on a logistic regression model. A total of 45,138 HIV serology tests were performed; 250 patients met inclusion criteria, comprising 84 (34%) HIV negative patients, 136 (54%) chronic infections, and 30 (12%) acute infections. The PP of a confirmed positive result increased with higher S/CO ratios, with a PP of 100% for a S/CO of 55 (95% CI 95-100). This study enables a more informed discussion of the probability of HIV infection, based on HIV serology S/CO thresholds, prior to a confirmatory result.
Asunto(s)
Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , VIH-1/inmunología , Anticuerpos Anti-VIH/sangre , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/epidemiología , Humanos , Mediciones Luminiscentes/métodos , Tamizaje Masivo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pruebas SerológicasRESUMEN
Continuous femoral nerve block (cFNB) is thought to increase the risk of falls after total knee arthroplasty (TKA). Previous studies have failed to consider the timing of cFNB removal in relation to inpatient falls. We investigated all inpatient falls after TKA over a 3-year period using our institutional safety report database. Ninety-five falls were reported from a total of 3745 patients. The frequency of falls after TKA persisted at a similar rate despite removal of cFNB and likely regression of femoral nerve block. Other modifiable risk factors may play a more prominent role in falls risk after TKA.
Asunto(s)
Accidentes por Caídas , Artroplastia de Reemplazo de Rodilla/efectos adversos , Nervio Femoral , Pacientes Internos , Articulación de la Rodilla/cirugía , Bloqueo Nervioso/efectos adversos , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Spinal cord transection leads to elimination of brain stem-derived monoamine fibers that normally synthesize most of the monoamines in the spinal cord, including serotonin (5-hydroxytryptamine, 5-HT) synthesized from tryptophan by enzymes tryptophan hydroxylase (TPH, synthesizing 5-hydroxytryptophan, 5-HTP) and aromatic l-amino acid decarboxylase (AADC, synthesizing 5-HT from 5-HTP). Here we examine whether spinal cord caudal to transection remains able to manufacture and metabolize 5-HT. Immunolabeling for AADC reveals that, while most AADC is confined to brain stem-derived monoamine fibers in spinal cords from normal rats, caudal to transection AADC is primarily found in blood vessel endothelial cells and pericytes as well as a novel group of neurons (NeuN positive and GFAP negative), all of which strongly upregulate AADC with injury. However, immunolabeling for 5-HT reveals that there is no detectable endogenous 5-HT synthesis in any structure in the spinal cord caudal to a chronic transection, including in AADC-containing vessels and neurons, consistent with a lack of TPH. In contrast, when we applied exogenous 5-HTP (in vitro or in vivo), AADC-containing vessels and neurons synthesized 5-HT, which contributed to increased motoneuron activity and muscle spasms (long-lasting reflexes, LLRs), by acting on 5-HT2 receptors (SB206553 sensitive) located on motoneurons (TTX resistant). Blocking monoamine oxidase (MAO) markedly increased the sensitivity of the motoneurons (LLR) to 5-HTP, more than it increased the sensitivity of motoneurons to 5-HT, suggesting that 5-HT synthesized from AADC is largely metabolized in AADC-containing neurons and vessels. In summary, after spinal cord injury AADC is upregulated in vessels, pericytes, and neurons but does not endogenously produce 5-HT, whereas when exogenous 5-HTP is provided AADC does produce functional amounts of 5-HT, some of which is able to escape metabolism by MAO, diffuse out of these AADC-containing cells, and ultimately act on 5-HT receptors on motoneurons.
Asunto(s)
Descarboxilasas de Aminoácido-L-Aromático/metabolismo , Serotonina/biosíntesis , Traumatismos de la Médula Espinal/metabolismo , Médula Espinal/metabolismo , Animales , Descarboxilasas de Aminoácido-L-Aromático/genética , Tronco Encefálico/metabolismo , Femenino , Neuronas Motoras/metabolismo , Especificidad de Órganos , Pericitos/metabolismo , Ratas , Serotonina/metabolismo , Serotonina/farmacología , Médula Espinal/citología , Médula Espinal/efectos de los fármacosRESUMEN
Thraustochytrids, a group of osmoheterotrophic marine protists, have recently gained increased attention owing to their spectacular biotechnological potentials. They possess enormous capability of producing omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and several other bioactive metabolites, known to have nutritional implications in human health. They have emerged lately as an efficient economic alternative compared with other fish and algal oil sources by virtue of their simpler PUFA profiles and cost-effective culture conditions. This review is an attempt to summarize the ecological significance of thraustochytrids with an emphasis on their cultured and uncultured diversity from various marine habitats accounted during the last few decades. Moreover, improved technologies such as media optimization in conjugation with metabolic engineering, adopted for biotechnological advancement of ω-3 products of thraustochytrids are highlighted with particular concern on the respective fatty acid biosynthetic pathways. One of the future prospects focuses on utilization of thraustochytrids for biodiesel production owing to their tremendous potentiality of yielding low carbon monounsaturated fatty acids (LC-MUFAs). However, there is utmost need of in-depth diversity assessments from various oceanic ecosystems in order to gain insight on potential thraustochytrids for ameliorated employment toward biotechnological applications.
Asunto(s)
Biotecnología/métodos , Ecosistema , Metabolismo de los Lípidos , Agua de Mar/parasitología , Estramenopilos/metabolismo , Organismos AcuáticosRESUMEN
OBJECTIVE: In rheumatoid arthritis (RA), quality indicators (QIs) are tools used to measure process of care. This study aimed to assess performance of selected QIs from the 2004 Arthritis Foundation's QI Set at 2 major sites of a university network of teaching hospitals. METHODS: The charts and electronic hospital records of 76 RA patients were audited to determine adherence to QIs. Logistic multivariate regression analyses were performed to investigate potential determinants of nonadherence and propose measures to facilitate better QI compliance, as a potential strategy towards RA care improvement. RESULTS: We identified consistent observance of QIs mandating prescription of disease-modifying antirheumatic drug therapy for all patients, drug adjustment with disease activity, prednisone tapering, and bisphosphonate therapy if indicated for patients on glucocorticoids. However, there was either lack of documentation or true inconsistent adherence to QIs dealing with radiograph performance, functional capacity assessment, and screening for hepatitis and tuberculosis before commencement of methotrexate and biologic agents, respectively. For the specific QIs analyzed, we did not find any definite independent associations with the studied variables. CONCLUSIONS: Our findings indicate that while there is frequent evidence for adherence to certain RA quality care standards at our centers, there is less compliance to others. Strategies to optimize the performance or documentation of those found most lacking, namely, functional capacity and screening for specific drug contraindications, could improve patient care. Radiographic disease monitoring, while lacking, may represent a move toward other more sensitive methods of RA progression detection, such as joint ultrasound. The inclusion of patient- and physician-derived information could help elucidate the reasons underlying nonadherence.
Asunto(s)
Artritis Reumatoide/terapia , Auditoría Clínica , Indicadores de Calidad de la Atención de Salud , Absorciometría de Fotón/estadística & datos numéricos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/epidemiología , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Difosfonatos/uso terapéutico , Femenino , Huesos del Pie/diagnóstico por imagen , Glucocorticoides/uso terapéutico , Huesos de la Mano/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Dimensión del Dolor , Examen Físico/estadística & datos numéricos , Prednisona/administración & dosificación , Quebec , Radiografía/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricosRESUMEN
We compared the performance of ID NOW™ COVID-19 assay nasal swabs with RT-PCR of nasopharyngeal swabs for SARS-CoV-2 in an outbreak setting, determining whether addition of RT-PCR of residual nasal swabs (rNS) (post ID NOW™ elution) would increase overall analytic sensitivity. Devices were placed at 2 long term and 1 acute care sites and 51 participants were recruited. Prospective paired nasopharyngeal and nasal samples were collected for RT-PCR and ID NOW™. ID NOW™ had a positive and negative categorical agreement of 86% and 93% compared to RT-PCR of nasopharyngeal swabs. Sensitivity and specificity of the ID NOW™ was 86% and 100%, positive and negative predictive value was 100% and 95% (COVID-19 positivity rate: 8%). Addition of rNS RT-PCR increased the positive and negative categorical agreement to 93% and 97%. Based on these results, we propose an alternative workflow which includes complementary testing of rNS on a secondary assay.
Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2/genética , Técnicas de Laboratorio Clínico/métodos , Prueba de COVID-19 , Estudios Prospectivos , Nasofaringe , Sensibilidad y EspecificidadRESUMEN
The residual stress plays an important role in composite flywheel rotors composed of filament windings. The fiber tension during high-prestressed winding is the main source of the rotor deformation and residual stress of composite layers. In this study, the effect of the winding tension gradient on deformation was monitored in real-time. Two types of in-plane winding tension fluctuation methods were developed to investigate the effect of tension on deformation. Online and offline measurements were performed for the strain acquisition. A wireless strain instrument was used for online deformation monitoring and a laser scanner was used for the offline surface reconstruction. Additionally, different filament winding strategies were carried out to improve the efficiency of the winding tension by finite element analysis. The results indicated that the deviation between numerical and experimental results was within 8%. Based on the proposed numerical method, the influence of the in-plane and out-of-plane winding tension gradient distributions on the rotation process of the H-shaped rotor was analyzed. An in-plane winding strategy with variable tension was developed, which increased the initial failure speed by 160%.
RESUMEN
Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2 -/-) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1 -/- mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis.
RESUMEN
The BioFire® COVID-19 Test and Respiratory Panel 2.1 (RP2.1) are rapid, fully automated assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs. In the case of the RP2.1, an additional 21 viral and bacterial pathogens can be detected. Both tests have received emergency use authorization from the U.S. Food & Drug Administration and Interim Order authorization from Health Canada for use in clinical laboratories. We evaluated the performance characteristics of these tests in comparison to a laboratory-developed real-time PCR assay targeting the viral RNA-dependent RNA polymerase and E genes. A total of 78 tests were performed using the BioFire COVID-19 Test, including 30 clinical specimens and 48 tests in a limit of detection study; 57 tests were performed using the RP2.1 for evaluation of SARS-CoV-2 detection, including 30 clinical specimens and 27 tests for limit of detection. Results showed 100% concordance between the BioFire assays and the laboratory-developed test for all clinical samples tested, and acceptable performance of both BioFire assays at their stated limits of detection. Conclusively, the BioFire COVID-19 Test and RP2.1 are highly sensitive assays that can be effectively used in the clinical laboratory for rapid SARS-CoV-2 testing.
Asunto(s)
Prueba de COVID-19/métodos , COVID-19/diagnóstico , Nasofaringe/virología , SARS-CoV-2/aislamiento & purificación , Prueba de COVID-19/normas , Técnicas de Laboratorio Clínico/métodos , Pruebas Diagnósticas de Rutina , Humanos , Límite de Detección , Reacción en Cadena de la Polimerasa Multiplex , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
15-Hydroxyeicosatetraenoic acid (15-HETE), a metabolic product of arachidonic acid (AA), plays an important role in pulmonary vascular smooth muscle remodeling. Although its effects on the apoptotic responses are known, the underlying mechanisms are still poorly understood. Since Akt is a critical regulator of cell survival and vascular remodeling, there may be a crosstalk between 15-HETE anti-apoptotic process and PI3K/Akt survival effect in rat pulmonary arterial smooth muscle cells (PASMCs). To test this hypothesis, we studied the effect of 15-HETE on cell survival and apoptosis using Western blot, cell viability measurement, nuclear morphology determination, TUNEL assay and mitochondrial potential analysis. We found that activation of the PI3K/Akt signaling system was necessary for the 15-HETE to suppress PASMC apoptosis and improve cell survival. Our results indicated that 15-HETE inhibited the apoptotic responses of PASMCs, including morphological alterations, mitochondrial depolarization and the expression apoptosis-specific proteins. These effects were likely to be mediated through the activation of PI3K/Akt. Two downstream signal molecules of PI3K/Akt were identified. Both FasL and Bad were down-regulated by 15-HETE and 15-HETE phosphorylated Bad. These changes depended on the PI3K/Akt signaling pathway in PASMCs. Thus a signal transduction pathway was demonstrated which is necessary for the effects of 15-HETE in protection PASMCs from apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Ácidos Hidroxieicosatetraenoicos/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Arteria Pulmonar/citología , Transducción de Señal/efectos de los fármacos , Animales , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proteína Ligando Fas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Ácidos Hidroxieicosatetraenoicos/química , Ácidos Hidroxieicosatetraenoicos/metabolismo , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar , Proteína Letal Asociada a bcl/metabolismoRESUMEN
A new species of Nanhaipotamon sp. Nov. was found from the west of Xiapu County, Fujian Province in April 2008. Holotype: male, carapace length 28.2 mm, breadth 35.6 mm, thickness 20.4 mm. Allotype, female, carapace length 22.6 mm, breadth 28.7 mm, thickness 20.4 mm. Male first pleopod reached beyond tubercle of abdominal lock, not reaching to suture of sternites 4/5. Subterminal segment was about 2.4 times as terminal segment, inner horn rounded to squarish, and its outer horn pointed to the upper part of abdomen. Morphologically, this new species is distinguishable to the similar species of freshwater crabs, such as N. formosanum, N. nonriense, and N. yongchunense.
Asunto(s)
Braquiuros/clasificación , Animales , Femenino , Agua Dulce , MasculinoRESUMEN
The ability to predict responsiveness to drugs in individual patients is limited. We hypothesized that integrating molecular information from databases would yield predictions that could be experimentally tested to develop transcriptomic signatures for specific drugs. We analyzed lung adenocarcinoma patient data from The Cancer Genome Atlas and identified a subset of patients in which xanthine dehydrogenase (XDH) expression correlated with decreased survival. We tested allopurinol, an FDA-approved drug that inhibits XDH, on human non-small-cell lung cancer (NSCLC) cell lines obtained from the Broad Institute Cancer Cell Line Encyclopedia and identified sensitive and resistant cell lines. We utilized the transcriptomic profiles of these cell lines to identify six-gene signatures for allopurinol-sensitive and allopurinol-resistant cell lines. Transcriptomic networks identified JAK2 as an additional target in allopurinol-resistant lines. Treatment of resistant cell lines with allopurinol and CEP-33779 (a JAK2 inhibitor) resulted in cell death. The effectiveness of allopurinol alone or allopurinol and CEP-33779 was verified in vivo using tumor formation in NCR-nude mice. We utilized the six-gene signatures to predict five additional allopurinol-sensitive NSCLC cell lines and four allopurinol-resistant cell lines susceptible to combination therapy. We searched the transcriptomic data from a library of patient-derived NSCLC tumors from the Jackson Laboratory to identify tumors that would be predicted to be sensitive to allopurinol or allopurinol + CEP-33779 treatment. Patient-derived tumors showed the predicted drug sensitivity in vivo. These data indicate that we can use integrated molecular information from cancer databases to predict drug responsiveness in individual patients and thus enable precision medicine.
Asunto(s)
Alopurinol/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Genómica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Análisis de Sistemas , Alopurinol/farmacología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/metabolismo , Neoplasias Pulmonares/patología , Ratones Desnudos , Fenotipo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Triazoles/farmacología , Triazoles/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hematopoietic stem/progenitor cells (HSPC) are characterized by their unique capacities of self-renewal and multi-differentiation potential. This second property makes them able to adapt their differentiation profile depending on the local environment they reach. Taking advantage of an animal model of peritonitis, induced by injection of the TLR-2 ligand, zymosan, we sought to study the relationship between bone marrow-derived hematopoietic stem/progenitor cells (BM-HSPCs) and innate lymphoid cells (ILCs) regarding their emergence and differentiation at the site of inflammation. Our results demonstrate that the strength of the inflammatory signals affects the capacity of BM-derived HSPCs to migrate and give rise in situ to ILCs. Both low- and high-dose of zymosan injections trigger the appearance of mature ILCs in the peritoneal cavity where the inflammation occurs. Herein, we show that only in low-dose injected mice, the recovered ILCs are dependent on an in situ differentiation of BM-derived HSPCs and/or ILC2 precursors (ILC2P) wherein high-dose, the stronger inflammatory environment seems to be able to induce the emergence of ILCs independently of BM-derived HSPCs. We suggest that a relationship between HSPCs and ILCs seems to be affected by the strength of the inflammatory stimuli opening new perspectives in the manipulation of these early hematopoietic cells.
Asunto(s)
Células Madre Hematopoyéticas/inmunología , Linfocitos/inmunología , Peritonitis/inmunología , Animales , Células de la Médula Ósea/citología , Diferenciación Celular , Movimiento Celular , Autorrenovación de las Células , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunidad Innata , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Nicho de Células Madre , ZimosanRESUMEN
One-hundred-and-sixteen Asian American college students viewed analogue videotapes in which an actress portraying a European American female "counselor" expressed cultural values that were either consistent or inconsistent with Asian culture to an actress portraying an Asian American female "client." In addition, the counselor either acknowledged racial differences or did not acknowledge racial differences with the client. The results showed that when the counselor expressed values that were inconsistent with Asian culture, the counselor who acknowledged racial differences was perceived to be more cross-culturally competent than the counselor who did not acknowledge racial differences. Also, the results showed that observer-participants' adherence to the value of conformity to norms was positively associated with their ratings of counselor credibility and crosscultural counseling competence. (PsycINFO Database Record (c) 2010 APA, all rights reserved).