Optical coherence tomography (OCT) is a promising tool for detecting micro channels, metal prints, defects and delaminations embedded in alumina and zirconia ceramic layers at hundreds of micrometers ...beneath surfaces. The effect of surface roughness and scattering of probing radiation within sample on OCT inspection is analyzed from the experimental and simulated OCT images of the ceramic samples with varying surface roughnesses and operating wavelengths. By Monte Carlo simulations of the OCT images in the mid-IR the optimal operating wavelength is found to be 4 µm for the alumina samples and 2 µm for the zirconia samples for achieving sufficient probing depth of about 1 mm. The effects of rough surfaces and dispersion on the detection of the embedded boundaries are discussed. Two types of image artefacts are found in OCT images due to multiple reflections between neighboring boundaries and inhomogeneity of refractive index.
The apicoplast is an essential plastid organelle found in Plasmodium parasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 ...from the "Malaria Box" library of growth-inhibitory antimalarial compounds as having specific activity against the apicoplast. MMV-08138 inhibition of blood-stage Plasmodium falciparum growth is stereospecific and potent, with the most active diastereomer demonstrating a 50% effective concentration (EC50) of 110 nM. Whole-genome sequencing of 3 drug-resistant parasite populations from two independent selections revealed E688Q and L244I mutations in P. falciparum IspD, an enzyme in the MEP (methyl-d-erythritol-4-phosphate) isoprenoid precursor biosynthesis pathway in the apicoplast. The active diastereomer of MMV-08138 directly inhibited PfIspD activity in vitro with a 50% inhibitory concentration (IC50) of 7.0 nM. MMV-08138 is the first PfIspD inhibitor to be identified and, together with heterologously expressed PfIspD, provides the foundation for further development of this promising antimalarial drug candidate lead. Furthermore, this report validates the use of the apicoplast chemical rescue screen coupled with target elucidation as a discovery tool to identify specific apicoplast-targeting compounds with new mechanisms of action.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to ...differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following transplantation into the brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and beta-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following brain transplantation in mouse ICH stroke model, B10 human MSCs integrate into host brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.
Absorbable wedge-shaped polydioxanone (PDO) sutures are currently available for facial rejuvenation, and they are extremely popular in the aesthetic clinics in Korea. Other than face lifting, threads ...also can be used for nonsurgical rhinoplasty. The Asian nose is typified by a flat nasal bridge, indistinct nasal dorsum, underprojected and broad nasal tip, and a short columella. In the past, Asian rhinoplasty mainly focused on dorsal augmentation. At present, augmentation of the nasal tip is very popular and is considered an important aspect of achieving a natural and balanced nose.
To describe a novel technique with PDO threads in nonsurgical rhinoplasty. In addition, the authors aimed to assess the overall safety and efficacy of nonsurgical rhinoplasty combining both fillers and threads.
A retrospective analysis was performed on Korean patients who received rhinoplasty with PDO threads and fillers. All participants underwent a single treatment session. The results were assessed objectively by 2 independent dermatologists using serial photography and subjectively based on the patients' satisfaction scores at 6-month follow-up.
A total of 31 patients were evaluated, and 93.5% considered the results satisfactory. Consensus ratings at the 6-month follow-up were largely categorized as very much improved (38.7%), much improved (35.5%), and improved (25.8%). An average increase of 6.3° (percentage increase by 7.6) in the nasolabial angle (p < .05) was measured at follow-up. The incidence of the complications was low, and the ones reported were minor.
Nonsurgical rhinoplasty combining PDO threads and fillers can be safe and effective, maintaining good results at 6 months after the procedure. Threads are especially useful for lifting-up the nasal tip, contributing to a more harmonious and pleasing nasal appearance by modifying the columella-labial angle.
•We describe state-of-the art fiber-based imaging modalities using various types of optical fibers.•Summarizes the advantages and limitations of optical fibers used for microendoscopic ...imaging.•Review imaging modalities of a number of fluorescence microendoscopes.
Optical fiber-based high-resolution fluorescence imaging techniques have promising applications in clinical practice and preclinical research using animals. Here we review the instrumentation and applications of microendoscopy based on various types of optical fibers. Single-mode fibers and double-clad fibers have been widely used for delivering light from light sources to tissues and collecting light from tissues to photodetectors. Coherent fiber bundles, cylindrical graded-index lenses, and multi-mode fibers have been employed in both beam-scanning and non-scanning microscopy. With continuing advances of optical fiber technologies, further innovations in optical microendoscopy are expected.
The tyrosine kinase WEE1 controls the timing of entry into mitosis in eukaryotes and its genetic deletion leads to pre-implantation lethality in mice. Here, we show that besides the premature mitotic ...entry phenotype, Wee1 mutant murine cells fail to complete mitosis properly and exhibit several additional defects that contribute to the deregulation of mitosis, allowing mutant cells to progress through mitosis at the expense of genomic integrity. WEE1 interacts with the anaphase promoting complex, functioning as a negative regulator, and the deletion of Wee1 results in hyper-activation of this complex. Mammary specific knockout mice overcome the DNA damage response pathway triggered by the mis-coordination of the cell cycle in mammary epithelial cells and heterozygote mice spontaneously develop mammary tumors. Thus, WEE1 functions as a haploinsufficient tumor suppressor that coordinates distinct cell division events to allow correct segregation of genetic information into daughter cells and maintain genome integrity.
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices ...for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype.
Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument.
Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets.
Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.
This study aims to analyze tire wear particulate matter (TWP) from tread rubber with different formulations and to compare the concentration of TWP with different wear devices. The TWP generated ...during the abrasion of truck and bus radial (TBR) tires were examined, and the effect of using different types of rubber and carbon black (CB) were investigated. When natural rubber (NR) was solely used as the tire tread rubber material, there was a higher concentration of 5-10 µm TWP. However, when the tread formulation consisted of NR mixed with butadiene rubber, the TWP concentration decreased. Changing the type of CB also reduced the amount of TWP in the 2.5 µm size range. The TWP concentration in the specimens increased with increasing speed and vertical load. The TWP generated during the abrasion tests using wear testers and tire simulators exhibited similar trends. These findings suggest that modifying tire tread formulations can effectively control the distribution and amount of TWP generation.
Background and Objectives
The prognostic value of obesity is unestablished for renal cell carcinoma. We assessed the age‐dependent prognostic value of body mass index (BMI) in a large multicenter ...cohort of patients with non‐metastatic clear cell renal cell carcinoma (nm‐cRCC).
Methods
This study evaluated 2092 patients with nm‐cRCC who underwent surgery with curative intent at five Korean institutions between 2001 and 2014.
Results
There was no significant difference in BMI between the young (<45 years) and older patients (≥45 years) (P = 0.398). Among older patients, high BMI (≥25 kg/m2) was associated with better 5‐year rates of recurrence‐free survival (RFS) and cancer‐specific survival (CSS) (P = 0.003 and 0.004, respectively), and multivariate analysis confirmed that high BMI was independently associated with better RFS and CSS (RFS hazard ratio HR: 0.617, P = 0.005; CSS HR: 0.588, P = 0.024). However, among young patients, there were no significant BMI‐related differences in the 5‐year RFS and CSS rates (P = 0.457 and 0.420, respectively), and high BMI was not independently associated with RFS or CSS (P = 0.822 and 0.749, respectively).
Conclusions
Among patients with nm‐cRCC, high BMI was associated with a favorable prognosis among older patients but not among young patients. Therefore, the relationship between obesity and nm‐cRCC prognosis might vary according to age.
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