RESUMEN
Porous substrate electroporation (PSEP) is a promising new method for intracellular delivery, yet fundamentals of PSEP are not well understood, especially the intermediate processes leading to delivery. PSEP is an electrical method, yet the relationship between PSEP and electrical impedance remains underexplored. In this study, a device capable of measuring impedance and performing PSEP is developed and the changes in transepithelial electrical impedance (TEEI) are monitored. These measurements show TEEI increases following PSEP, unlike other electroporation methods. The authors then demonstrate how cell culture conditions and electrical waveforms influence this response. More importantly, TEEI response features are correlated with viability and delivery efficiency, allowing prediction of outcomes without fluorescent cargo, imaging, or image processing. This label-free delivery also allows improved temporal resolution of transient processes following PSEP, which the authors expect will aid PSEP optimization for new cell types and cargos.
Asunto(s)
Impedancia Eléctrica , Electroporación , Electroporación/métodos , Porosidad , Animales , Humanos , Supervivencia CelularRESUMEN
BACKGROUND: Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment. METHODS: The biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing. RESULTS: MNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression. CONCLUSION: Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.
RESUMEN
PURPOSE: For asymptomatic non-functioning pituitary adenomas (NFPAs), conservative approaches such as observation are preferred. However, some NFPAs exhibit poor prognoses. Thus, the purpose of this study was to investigate clinicopathological characteristics of tumors for identifying those with unfavorable prognoses. METHODS: A total of 125 patients with NFPAs who underwent surgery between November 2017 and December 2022 at our institution were retrospectively analyzed. Clinical, radiological, and pathological data, including hormone profiles, tumor size, presence of cavernous sinus invasion, and Ki-67 index levels, were reviewed. High-risk PAs were identified according to 2022 WHO criteria. Statistical analyses including Kaplan-Meier survival analysis and Cox regression were performed to evaluate factors associated with tumor progression or recurrence. RESULTS: A high-risk group demonstrated a significantly higher rate of tumor progression/recurrence than a low-risk group (p-value = 0.004). In multivariate analysis, the high-risk group at the time of diagnosis remained as an independent prognostic factor for NFPAs (p-value = 0.0148). The high-risk group also had a higher percentage of younger patients (80.0% in the high-risk group vs. 62.2% in the low-risk group, p-value = 0.016) and female patients (91.4% vs. 34.4%, p< 0.001). The presence of cavernous sinus invasion and higher Ki-67 index levels were more commonly observed in the high-risk group, although these factors did not significantly impact the overall prognosis. CONCLUSION: Our findings indicate that patients with high-risk NFPAs have a more aggressive disease course and a higher rate of progression or recurrence. This high-risk group has higher prevalence of younger and female patients. They may benefit from closer monitoring and possibly more aggressive treatment approaches.
RESUMEN
PURPOSE: Recently, reduced-dose whole-brain radiotherapy (WBRT) has been used to treat primary central nervous system lymphoma (PCNSL). However, whether reduced-dose WBRT is also an acceptable option for curative or salvage purposes has not yet been reported. We analyzed the clinical outcomes of patients with PCNSL who received radiotherapy for curative or salvage purposes and compared the clinical outcomes according to the WBRT dose. METHODS: A total of 66 patients were divided into two groups: those treated with 30 Gy (2 Gy per fraction) or less WBRT (low-dose WBRT, n = 34) and those treated with more than 30 Gy WBRT (high-dose WBRT, n = 32). The median WBRT dose was 25.2 and 49.6 Gy in low-dose and high-dose WBRT groups, respectively. The median total radiotherapy dose, including the boost dose, was 50 Gy (range, 36.0-55.8 Gy). RESULTS: The 3-year overall survival and progression-free survival were 77.8% and 29.8%, respectively. Intracranial relapse occurred in 31 patients (47.0%) at a median of 27 months after RT. Overall survival and progression-free survival did not differ between the two groups. The 3-year intracranial disease control rate did not differ between the two groups (35.2% vs. 41.6%, p = 0.300). Grade 3 or higher neurological toxicities were observed in six patients, of whom five were in the high-dose WBRT group. CONCLUSION: Reduced-dose WBRT in curative and salvage treatments for PCNSL had no significant negative effect on the intracranial disease control rate or survival. Therefore, without impaired efficacy, use of reduced-dose WBRT appears promising for reduction of neurotoxicity.
Asunto(s)
Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Linfoma , Humanos , Neoplasias del Sistema Nervioso Central/patología , Linfoma/patología , Recurrencia Local de Neoplasia , Neoplasias Encefálicas/radioterapia , Encéfalo/patología , Irradiación Craneana/efectos adversosRESUMEN
BACKGROUND: Chronic subdural hematoma (CSDH) is a common clinical situation in neurosurgical practice, but the optimal treatment option is controversial. This study aimed to evaluate the effect of cholesterol-lowering medications on and how they affected the prognoses of CSDH patients. METHODS: In this multi-institutional observational study performed in Korea, data from recently treated CSDH patients were gathered from 5 hospitals. A total of 462 patients were collected from March 2010 to June 2021. Patient clinical characteristics, history of underlying diseases and their treatments, radiologic features, and surgical outcomes were analyzed. RESULTS: Seventy-five patients experienced recurrences, and 62 had reoperations after the initial burr hole surgery. Among these, 15 patients with recurrences and 12 with reoperations were taking cholesterol-lowering medications. However, the use of medications did not significantly affect recurrence or reoperation rates (P = 0.350, P = 0.336, respectively). When analyzed by type of medication, no clinically relevant differences in total cholesterol (TC), triglyceride (TG), or low-density lipoprotein cholesterol (LDL-C) levels were identified. The combination of a statin drug and ezetimibe significantly elevated high-density lipoprotein cholesterol (HDL-C) levels (P = 0.004). TC, LDL-C, and TG levels did not significantly affect patient prognoses. However, HDL-C levels and recurrence (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.94-0.99; p = 0.010) were negatively correlated. An HDL-C level of 42.50 mg/dL was identified as the threshold for recurrence and reoperation. CONCLUSIONS: In this study, using cholesterol-lowering medications did not significantly impact the prognosis of patients who underwent surgical management for a chronic subdural hematoma. However, the findings showed that the higher the HDL-C level, the lower the probability of recurrence and reoperation.
Asunto(s)
Hematoma Subdural Crónico , Humanos , Hematoma Subdural Crónico/tratamiento farmacológico , Hematoma Subdural Crónico/cirugía , HDL-Colesterol , LDL-Colesterol , Estudios Retrospectivos , Recurrencia , República de Corea , Drenaje , Resultado del TratamientoRESUMEN
Confined active nematics exhibit rich dynamical behavior, including spontaneous flows, periodic defect dynamics, and chaotic "active turbulence." Here, we study these phenomena using the framework of exact coherent structures, which has been successful in characterizing the routes to high Reynolds number turbulence of passive fluids. Exact coherent structures are stationary, periodic, quasiperiodic, or traveling wave solutions of the hydrodynamic equations that, together with their invariant manifolds, serve as an organizing template of the dynamics. We compute the dominant exact coherent structures and connecting orbits in a preturbulent active nematic channel flow, which enables a fully nonlinear but highly reduced-order description in terms of a directed graph. Using this reduced representation, we compute instantaneous perturbations that switch the system between disparate spatiotemporal states occupying distant regions of the infinite-dimensional phase space. Our results lay the groundwork for a systematic means of understanding and controlling active nematic flows in the moderate- to high-activity regime.
RESUMEN
Non-colloidal suspensions undergoing dipolar interactions in an electric field have been extensively studied and are also known as smart materials as they share similarities with electrorheological (ER) fluids. Although the macroscopic responses are well-documented, the multiscale nature of such suspensions is still lacking. In this study, a large-scale Stokesian dynamics simulation is used to investigate the structural formation of such suspensions in an electric field up to highly concentrated regimes across different length scales: from particle-level (microscale) to particle cluster-level (mesoscale) and stress response-level (macroscale). It is observed that at a volume fraction of Ï ≈ 30%, the steady-state structures are the most isotropic at the microscale, but at the macroscale, their normal stress fields are the most anisotropic. Interestingly, these structures are also the most heterogeneous at both the microscale and mesoscale. Furthermore, the effects of confinement on the multiscale responses are explored, revealing that there could be a strong link between the mesoscale and macroscale. This multiscale nature can offer the potential for precisely controlling or designing ER fluids in practical applications.
RESUMEN
OBJECTIVES: To evaluate the additional prognostic value of multiparametric MR-based radiomics in patients with glioblastoma when combined with conventional clinical and genetic prognostic factors. METHODS: In this single-center study, patients diagnosed with glioblastoma between October 2007 and December 2019 were retrospectively screened and grouped into training and test sets with a 7:3 distribution. Segmentations of glioblastoma using multiparametric MRI were performed automatically via a convolutional-neural network. Prognostic factors in the clinical model included age, sex, type of surgery/post-operative treatment, and tumor location; those in the genetic model included statuses of isocitrate dehydrogenase-1 mutation and O-6-methylguanine-DNA-methyltransferase promoter methylation. Univariate and multivariate Cox proportional hazards analyses were performed for overall survival (OS) and progression-free survival (PFS). Integrated time-dependent area under the curve (iAUC) for survival was calculated and compared between prognostic models via the bootstrapping method (performances were validated with prediction error curves). RESULTS: Overall, 120 patients were included (training set, 85; test set, 35). The mean OS and PFS were 25.5 and 18.6 months, respectively. The prognostic performances of multivariate models improved when radiomics was added to the clinical model (iAUC: OS, 0.62 to 0.73; PFS, 0.58 to 0.66), genetic model (iAUC: OS, 0.59 to 0.67; PFS, 0.59 to 0.65), and combined model (iAUC: OS, 0.65 to 0.73; PFS, 0.62 to 0.67). In the test set, the combined model (clinical, genetic, and radiomics) demonstrated robust validation for risk prediction of OS and PFS. CONCLUSIONS: Radiomics increased the prognostic value when combined with conventional clinical and genetic prognostic models for OS and PFS in glioblastoma patients. KEY POINTS: ⢠CNN-based automatic segmentation of glioblastoma on multiparametric MRI was useful in extracting radiomic features. ⢠Patients with glioblastoma with high-risk radiomics scores had poor overall survival (hazards ratio 8.33, p < 0.001) and progression-free survival (hazards ratio 3.76, p < 0.001). ⢠MR-based radiomics improved the survival prediction when combined with clinical and genetic factors (overall and progression-free survival iAUC from 0.65 to 0.73 and 0.62 to 0.67, respectively; both p < 0.001).
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Humanos , Imagen por Resonancia Magnética , Pronóstico , Estudios RetrospectivosRESUMEN
The tropolone-bearing sesquiterpenes juniperone A (1) and norjuniperone A (2) were isolated from the folk medicinal plant Juniperus chinensis, and their structures were determined by a combination of spectroscopic and crystallographic methods. Photojuniperones A1 (3) and A2 (4), bearing bicyclo[3,2,0]heptadienones derived from tropolone, were photochemically produced and structurally identified by spectroscopic methods. Predicted by the machine learning-based assay, 1 significantly inhibited the action of tyrosinase. The new compounds also inhibited lipid accumulation and enhanced the extracellular glycerol excretion.
Asunto(s)
Juniperus/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Sesquiterpenos/farmacología , Tropolona/farmacología , Animales , Células Hep G2 , Humanos , Melanocitos/efectos de los fármacos , Ratones , Estructura Molecular , Fotoquímica , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Plantas Medicinales/química , República de Corea , Sesquiterpenos/aislamiento & purificación , Tropolona/aislamiento & purificación , Madera/químicaRESUMEN
BACKGROUND: With the developments in the arthroscopic technique, anterior cruciate ligament (ACL) remnant-preserving reconstruction is gradually gaining attention with respect to improving proprioception and enhancing early revascularization of the graft. To evaluate the mechanical pull-out strength of three different methods for remnant-preserving and re-tensioning reconstruction during ACL reconstruction. METHODS: Twenty-seven fresh knees from mature pigs were used in this study. Each knee was dissected to isolate the femoral attachment of ACL and cut the attachment. An MTS tensile testing machine with dual-screw fixation clamp with 30° flexion angle was used. The 27 specimens were tested after applying re-tensioning sutures with No. 0 polydioxanone (PDS), using the single stitch (n = 9), loop stitch (n = 9), and triple stitch (n = 9) methods. We measured the mode of failure, defined as (1) ligament failure (longitudinal splitting of the remnant ACL) or (2) suture failure (tearing of the PDS stitch); load-to-failure strength; and stiffness for the three methods. Kruskal-Wallis test and Mann-Whitney U-test were used to compare the variance of load-to-failure strength and stiffness among the three groups. RESULTS: Ligament failure occurred in all cases in the single stitch group and in all but one case in the triple stitch group. Suture failure occurred in all cases in the loop stitch group and in one case in the triple stitch group. The load-to-failure strength was significantly higher with loop stich (91.52 ± 8.19 N) and triple stitch (111.1 ± 18.15 N) than with single stitch (43.79 ± 11.54 N) (p = 0.002). With respect to stiffness, triple stitch (2.50 ± 0.37 N/mm) yielded significantly higher stiffness than the other methods (p = 0.001). CONCLUSIONS: The results suggested that loop stitch or triple stitch would be a better option for increasing the mechanical strength when applying remnant-preserving and re-tensioning reconstruction during ACL reconstruction.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Animales , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Humanos , Articulación de la Rodilla/cirugía , PorcinosRESUMEN
Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble-mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self-assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε-caprolactone), poly(lactic-co-glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto-responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.
Asunto(s)
Nanofibras , Animales , Biomimética , Gelatina , Microesferas , Poliésteres , Polímeros , Ratas , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Thirteen coumarins (1-13), including five new compounds (1-5), were isolated from the folk medicinal plant Poncirus trifoliata. Combined spectroscopic analyses revealed that coumarins 1-4 are bis-isoprenylated coumarins with diverse oxidation patterns, while 5 is an enantiomeric di-isoprenylated coumarin. The absolute configurations of the stereogenic centers in the isoprenyl chains were assigned through MTPA and MPA methods, and those of the known compounds triphasiol (6) and ponciol (7) were also assigned using similar methods. These coumarins inhibited significantly Staphylococcus aureus-derived sortase A (SrtA), a transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall in Gram-positive bacteria. The present results obtained indicated that the bioactivity and underlying mechanism of action of these coumarins are associated with the inhibition of SrtA-mediated S. aureus adhesion to eukaryotic cell matrix proteins including fibrinogen and fibronectin, thus potentially serving as SrtA inhibitors.
Asunto(s)
Aminoaciltransferasas/antagonistas & inhibidores , Proteínas Bacterianas/antagonistas & inhibidores , Cumarinas/farmacología , Plantas Medicinales , Poncirus , Cisteína Endopeptidasas , Fibrinógeno , Fibronectinas , Bacterias Grampositivas , Proteínas de la Membrana , Estructura Molecular , Infecciones Estafilocócicas , Staphylococcus aureusRESUMEN
Isocadiolides A-H (1-8) and cadiolide N (9), new polybrominated aromatic compounds, were isolated from a Korean Synoicum sp. ascidian. On the basis of the results of extensive spectroscopic analyses, these compounds possessed tris-bromohydroxyphenyl moieties as a common structural motif, while their cores varied [cyclopentenedione (1-5), dihydrofuran (6 and 7), pyranone (8), and furanone (9)], reflecting different extents of rearrangement and oxidation. Several of these compounds exhibited weak antibacterial activities and moderate abilities to inhibit the microbial enzymes sortase A and isocitrate lyase.
Asunto(s)
Aminoaciltransferasas/química , Antibacterianos/química , Proteínas Bacterianas/química , Cisteína Endopeptidasas/química , Isocitratoliasa/química , Bifenilos Polibrominados/química , Bifenilos Polibrominados/farmacología , Urocordados/química , Animales , Antibacterianos/farmacología , Isocitratoliasa/metabolismo , Estructura Molecular , Bifenilos Polibrominados/aislamiento & purificaciónRESUMEN
Skin is an important barrier to protect the body from environmental stress. However, exposure to ultraviolet radiation (UV) and various environmental oxidative stresses can cause skin inflammation. Cyclooxygenase-2 (COX-2) is an inducible enzyme that mediates the formation of prostaglandin E2 (PGE2) against internal and external inflammatory stimulations. Therefore, the inhibition of COX-2 is an important approach to maintain skin health and prevent skin inflammation and carcinogenesis. Topsentin, a bis(indolyl)imidazole alkaloid isolated from the marine sponge Spongosorites genitrix, has been reported to exhibit anti-tumor and anti-microbial activities. However, the effect of topsentin on skin inflammation and its underlying molecular mechanism has not been elucidated. In the present study, we identified the photoprotective effects of topsentin on UVB irradiated human epidermal keratinocyte HaCaT cells. Topsentin suppresses COX-2 expression and its upstream signaling pathways, AP-1 and MAPK. Furthermore, topsentin inhibits miR-4485, a new biomarker selected from a microarray, and its target gene tumor necrosis factor alpha induced protein 2 (TNF-α IP2). The photoprotective effect of topsentin was also confirmed in a reconstructed human skin model. These findings suggest that topsentin may serve as a potential candidate for cosmetic formulations with skin inflammatory-mediated disorder.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Imidazoles/farmacología , Indoles/farmacología , Poríferos , Protectores contra Radiación/farmacología , Animales , Células Epidérmicas , Queratinocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Piel , Rayos UltravioletaRESUMEN
Six new bis(indole) alkaloids (1-6) along with eight known ones of the topsentin class were isolated from a Spongosorites sp. sponge of Korea. Based on the results of combined spectroscopic analyses, the structures of spongosoritins A-D (1-4) were determined to possess a 2-methoxy-1-imidazole-5-one core connecting the indole moieties, and these were linked by a linear urea bridge for spongocarbamides A (5) and B (6). The absolute configurations of spongosoritins were assigned by electronic circular dichroism (ECD) computation. The new compounds exhibited moderate inhibition against transpeptidase sortase A and weak inhibition against human pathogenic bacteria and A549 and K562 cancer cell lines.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Alcaloides Indólicos/farmacología , Poríferos/metabolismo , Células A549 , Aminoaciltransferasas/antagonistas & inhibidores , Aminoaciltransferasas/metabolismo , Animales , Antibacterianos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Bacterias/efectos de los fármacos , Bacterias/enzimología , Bacterias/crecimiento & desarrollo , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Supervivencia Celular/efectos de los fármacos , Cisteína Endopeptidasas/metabolismo , Hongos/efectos de los fármacos , Hongos/crecimiento & desarrollo , Humanos , Alcaloides Indólicos/aislamiento & purificación , Células K562 , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Relación Estructura-ActividadRESUMEN
OBJECTIVE: This paper proposes a virtual reality (VR) haptic simulator with realistic instruments, an exchangeable patient-specific three-dimensional (3D)-printed external nostril and a caudal septum model to facilitate real surgical motion for training in endoscopic sinus and skull-base surgery. STUDY DESIGN AND SETTING: industry-academy cooperation development model METHODS:: The VR simulator consists of the main simulator body, a monitor, an endoscope device, 2 haptic devices, an endoscope holder support fixture, and a pair of pedals. The location of the endoscope device is determined by an electromagnetic sensor. Two haptic devices are located so as to prevent mutual interference during application of the two-nostrils/four-hands technique for endoscopic skull-base surgery. The pedals were used for select surgical instrument and endoscopes, and operate microdebriders or microdrill. An exchangeable patient-specific external nostril and caudal septum model was created using material that mimics the texture of human tissue and a 3D printer. Graphics were rendered using Unity 3D, to which the Simulation Open Framework Architecture (SOFA) physics engine can be bolted on using the Unity3d plug-in. RESULTS: This VR haptic simulator enables performance of basic endoscopic sinus surgeries (eg, maxillary sinus antrostomy, ethmoidectomy, and frontostomy), as well as endoscopic endonasal transsphenoidal (including sphenoidotomy) and transclival approaches. CONCLUSION: VR haptic simulators can improve the skill and confidence of surgical trainees by allowing them to accrue experience in various tasks under different conditions. The simulator introduced here comprises novel technologies and provides a realistic training environment for endoscopic sinus and skull-base surgery.
Asunto(s)
Cavidad Nasal/cirugía , Senos Paranasales/cirugía , Base del Cráneo/cirugía , Simulación por Computador , Humanos , Cavidad Nasal/diagnóstico por imagen , Neuroendoscopía , Procedimientos Neuroquirúrgicos , Senos Paranasales/diagnóstico por imagen , Impresión Tridimensional , Base del Cráneo/diagnóstico por imagen , Realidad VirtualRESUMEN
Recent direct numerical simulations (DNS) and experiments in turbulent channel flow have found intermittent low- and high-drag events in Newtonian fluid flows, at Reτ=uτh/ν between 70 and 100, where uτ, h and ν are the friction velocity, channel half-height and kinematic viscosity, respectively. These intervals of low-drag and high-drag have been termed "hibernating" and "hyperactive", respectively, and in this paper, a further investigation of these intermittent events is conducted using experimental and numerical techniques. For experiments, simultaneous measurements of wall shear stress and velocity are carried out in a channel flow facility using hot-film anemometry (HFA) and laser Doppler velocimetry (LDV), respectively, for Reτ between 70 and 250. For numerical simulations, DNS of a channel flow is performed in an extended domain at Reτ = 70 and 85. These intermittent events are selected by carrying out conditional sampling of the wall shear stress data based on a combined threshold magnitude and time-duration criteria. The use of three different scalings (so-called outer, inner and mixed) for the time-duration criterion for the conditional events is explored. It is found that if the time-duration criterion is kept constant in inner units, the frequency of occurrence of these conditional events remain insensitive to Reynolds number. There exists an exponential distribution of frequency of occurrence of the conditional events with respect to their duration, implying a potentially memoryless process. An explanation for the presence of a spike (or dip) in the ensemble-averaged wall shear stress data before and after the low-drag (or high-drag) events is investigated. During the low-drag events, the conditionally-averaged streamwise velocities get closer to Virk's maximum drag reduction (MDR) asymptote, near the wall, for all Reynolds numbers studied. Reynolds shear stress (RSS) characteristics during these conditional events are investigated for Reτ = 70 and 85. Except very close to the wall, the conditionally-averaged RSS is higher than the time-averaged value during the low-drag events.
RESUMEN
BACKGROUND: Brain metastasis is a rare event in patients with hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors and determine the outcomes of patients with brain metastases from HCC. METHODS: About 86 patients with brain metastases (0.6%) from HCC were identified from two institutions; of them, 32 underwent tumor-removing surgery or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT) (group 1), 30 had WBRT alone (group 2), and 24 received conservative treatment (group 3). Estimates for overall survival (OS) after brain metastases were determined, and clinical prognostic factors were identified. RESULTS: The median OS after development of brain metastases was 50 days. About 75 (87.2%) patients had lung metastases at the time of brain metastasis diagnosis. Group 1 showed better OS, followed by group 2 and group 3, sequentially (p < 0.001). Univariate analyses showed that treatment with curative intent (surgery or SRS), Child-Pugh class A, alpha-fetoprotein level < 400 ng/ml, and recursive partitioning analysis classification I or II were associated with improved survival (p < 0.001, 0.002, 0.029, and 0.012, respectively). Multivariate analysis showed that treatment with curative intent and Child-Pugh class A was associated with improved OS (p < 0.001 and 0.009, respectively). CONCLUSION: Although the overall prognosis of patients with brain metastases from HCC is extremely poor, patients actively treated with surgery or radiosurgery have prolonged survival, suggesting that interventions to control intracranial disease are important in these patients.
Asunto(s)
Neoplasias Encefálicas/mortalidad , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/mortalidad , Radiocirugia/mortalidad , Adulto , Anciano , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
This research demonstrates that a surface plasmon resonance (SPR) imaging technique can effectively measure full-field nanoscale thickness of a liquid water film filled in the receding contact-induced nano-channel. To the authors' knowledge this has not been demonstrated previously. Experimental calibration has been conducted by measuring surface plasmon resonance reflectance depending on the piezometer-controlled water nano-film thickness and comparing the experimental results with the theoretical calculations to show very good agreement. The measured full-field thickness profiles significantly visualize the three-dimensional nano-channel formation filled with liquid water film. It shows that the sensitivity and the resolution in thickness measurement are estimated as 1.21 pixel gray level/nm and 2.5 nm, respectively. The experimentally observed resolution is around 10 nm given the uncertainty in the demonstrated full-field mapping of thickness. From this research, it is demonstrated that SPR imaging successfully measures the thickness of ultrathin liquid film especially below 85 nm in full-field under normal conditions and can effectively characterize the three-dimensional nano-channel formation during the receding contact process.
RESUMEN
The surface activated bonding (SAB) method generally has the advantage of high bonding strength, low contact resistance, and high microstructural stability at room temperature. In this study, Ti-Al laminates were produced by surface activated bonding with aluminum and titanium foils. Heat treatment was conducted at the temperature range from 200 to 550 °C in vacuum. The bonding strength Ti-Al laminates was measured by a peel test, and the interfacial characteristics were investigated microstructural observation. The results showed that the bonding strength was the highest with heat treatment at 400 °C, microstructure observation revealed that the bonding strength of the Ti-Al laminate was influenced by the interfacial characteristics.