In the present study, we investigated the behavior of an amorphous carbon film covering a Mo grid at high temperature. It was found that metastable nanosized particles were formed on the carbon film ...at 400°C. They finally became nanosized α-Mo2C crystals with an average size of 3.5nm at 700°C. Moreover, modification of the amorphous carbon support film was observed. High-resolution TEM images showed that the carbon film was transformed to irregular and disordered lamellar structures at 300°C and to short-range ordered and crystallized structures at 700°C. Based on these experimental results, we suggest selecting suitable metal grids and support films for the TEM specimen preparation and performing a chemical analysis of nanostructure materials in in situ heating experiment. Finally, it is expected that these results will be helpful for the appropriate experimental designs for the in situ TEM studies.
► Amorphous carbon film covering a Mo grid was investigated by the in situ TEM technique. ► Unexpected nanosized α-Mo2C crystals were formed at 700°C. ► The amorphous carbon film was transformed into the crystalline phase during the in situ heating process.
SIACI of bevacizumab has emerged as a promising novel therapy in the treatment of recurrent GB. This study assessed the potential of (1)H-MRS as an adjunctive technique in detecting metabolic changes ...reflective of antiproliferative effects of targeted infusion of bevacizumab in the treatment of GB.
Eighteen patients enrolled in a phase I/II study of SIACI of bevacizumab for treatment of recurrent GB were included. Concurrent MR imaging and (1)H-MRS scans were performed before and after treatment. Five distinct morphologic ROIs were evaluated for structural and metabolic changes on MR imaging and (1)H-MRS, which included enhancing, nonenhancing T2 hyperintense signal abnormality, and multiple control regions. Pre- and post-SIACI of bevacizumab peak areas for NAA, tCho, tCr, as well as tCho/tCr and tCho/NAA ratios, were derived for all 5 ROIs and compared using the Wilcoxon signed-rank test.
A significant median decrease of 25.99% (range -55.76 to 123.94; P = .006) in tCho/NAA was found post-SIACI of bevacizumab relative to pretreatment values in regions of enhancing disease. A trend-level significant median decrease of 6.45% (range -23.71 to 37.67; P = .06) was noted in tCho/NAA posttreatment in regions of nonenhancing T2-hyperintense signal abnormality.
The results of this (1)H-MRS analysis suggest that GB treatment with SIACI of bevacizumab may be associated with a direct antiproliferative effect, as demonstrated by significant reductions of tCho/NAA after the intervention.
Few studies are available that compare PBSC and BM from unrelated donors, especially in adult high-risk ALL. To determine which graft source is superior in adult high-risk ALL, we analyzed the ...long-term outcomes of 106 consecutive transplants from 8/8-matched or 7/8-matched unrelated donors (38 PBSC vs 68 BM). All patients received a uniform strategy of pre-transplant therapy, myeloablative conditioning and GVHD prophylaxis. At 5 years, PBSC transplants showed higher incidence of chronic GVHD than did BM transplants (74.3% vs 46.7%, P=0.001). PBSC transplants showed outcomes comparable to those of BM transplants for relapse (23.7% vs 28.1%), non-relapse mortality (18.4% vs 25.0%), disease-free survival (57.9% vs 46.9%) and OS (57.9% vs 50.0%). In a separate comparison of outcomes between the two graft sources according to the presence of a Ph chromosome, no significant advantage of PBSC over BM was found in both subgroups of patients. Our data suggest that the outcomes of unrelated donor transplantation are similar between PBSC and BM in adult high-risk ALL. Whether PBSC should be the preferred graft source for a specific subgroup of adult ALL needs to be further investigated.
We present the first microlensing candidate for a free-floating exoplanet-exomoon system, MOA-2011-BLG-262, with a primary lens mass of M sub(host) ~ 4 Jupiter masses hosting a sub-Earth mass moon. ...The argument for an exomoon hinges on the system being relatively close to the Sun. The data constrain the product M sub(L)pi sub(rel) where M sub(L) is the lens system mass and pi sub(rel) is the lens-source relative parallax. If the lens system is nearby (large pi sub(rel)), then M sub(L) is small (a few Jupiter masses) and the companion is a sub-Earth-mass exomoon. The best-fit solution has a large lens-source relative proper motion, mu sub(rel) = 19.6 + or - 1.6 mas yr super(-1), which would rule out a distant lens system unless the source star has an unusually high proper motion. However, data from the OGLE collaboration nearly rule out a high source proper motion, so the exoplanet+exomoon model is the favored interpretation for the best fit model. However, there is an alternate solution that has a lower proper motion and fits the data almost as well. This solution is compatible with a distant (so stellar) host. A Bayesian analysis does not favor the exoplanet+exomoon interpretation, so Occam's razor favors a lens system in the bulge with host and companion masses of M sub(host) = 0.12 super(+0.19) sub(-0.06) M sub(middot in circle) and m sub(comp) = 18 super(+28) sub(-10) M sub(+ in circle), at a projected separation of a sub(perpendicular) = 0.84 super(+0.25) sub(-0.14) AU. The existence of this degeneracy is an unlucky accident, so current microlensing experiments are in principle sensitive to exomoons. In some circumstances, it will be possible to definitively establish the mass of such lens systems through the microlensing parallax effect. Future experiments will be sensitive to less extreme exomoons.
Human embryonic stem (hES) cells, due to their capacity of multipotency and self‐renewal, may serve as a valuable experimental tool for human developmental biology and may provide an unlimited cell ...source for cell replacement therapy. The purpose of this study was to assess the developmental potential of hES cells to replace the selectively lost midbrain dopamine (DA) neurons in Parkinson's disease. Here, we report the development of an in vitro differentiation protocol to derive an enriched population of midbrain DA neurons from hES cells. Neural induction of hES cells co‐cultured with stromal cells, followed by expansion of the resulting neural precursor cells, efficiently generated DA neurons with concomitant expression of transcriptional factors related to midbrain DA development, such as Pax2, En1 (Engrailed‐1), Nurr1, and Lmx1b. Using our procedure, the majority of differentiated hES cells (> 95%) contained neuronal or neural precursor markers and a high percentage (> 40%) of TuJ1+ neurons was tyrosine hydroxylase (TH)+, while none of them expressed the undifferentiated ES cell marker, Oct 3/4. Furthermore, hES cell‐derived DA neurons demonstrated functionality in vitro, releasing DA in response to KCl‐induced depolarization and reuptake of DA. Finally, transplantation of hES‐derived DA neurons into the striatum of hemi‐parkinsonian rats failed to result in improvement of their behavioral deficits as determined by amphetamine‐induced rotation and step‐adjustment. Immunohistochemical analyses of grafted brains revealed that abundant hES‐derived cells (human nuclei+ cells) survived in the grafts, but none of them were TH+. Therefore, unlike those from mouse ES cells, hES cell‐derived DA neurons either do not survive or their DA phenotype is unstable when grafted into rodent brains.
In chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD ...development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD.
The study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI), lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL.
The mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3%) and genotype 1F-2 (27.4%) were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL) and higher in those with genotype 1F-1S (estimated =4.08 ng/mL). The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41). Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61%) and lower in those with genotype 1F-2 (estimated =-3.31%). The 6-minute walking distance was shorter for patients with the GC1F variant (estimated =-38.91 m) and longer for those with the GC2 variant (estimated =26.98 m). The emphysema index was higher for patients with the GC1S variant (estimated =6.56%) and genotype 1F-1S (estimated =9.86%), regardless of the vitamin D level.
The GC2 variant is a risk factor for vitamin D deficiency, and genotype 1F-1S is a protective factor against vitamin D deficiency. GC polymorphisms and vitamin D deficiency correlate with clinical outcomes for Korean patients with COPD.
Acute GVHD (aGVHD) is an important risk factor for predicting the incidence or severity of chronic GVHD (cGVHD). Transplant outcome can be influenced by the onset time of aGVHD in patients who have ...received allogeneic PBSC transplants (PBSCTs). The medical records of 134 patients who survived more than 3 months after myeloablative allogeneic PBSCT were retrospectively reviewed. In all, 38 patients (28.4%) developed grade II-IV aGVHD before day +28 (early aGVHD) and 25 patients (18.7%) after day +28 (late aGVHD). The 5-year cumulative incidence of cGVHD was 78.9% in the early-aGVHD group and 56.6% in the late-aGVHD group (P=0.034). The 5-year OS was 51.0% for the early-aGVHD and 80.8% for the late-aGVHD group (P=0.406). Infection was the primary cause of death for the early-aGVHD group (51.4 vs 16.7%, P=0.017), whereas relapse of the primary disease was higher among the patients with late aGVHD, although this was statistically insignificant (58.3 vs 25.7%, P=0.309). In a multivariate analysis, early aGVHD was identified as a risk factor for developing cGVHD (hazard ratio (HR) 2.278, P=0.004). The development of aGVHD early after allogeneic PBSCT increased the risk of cGVHD and infection-related death rate when compared with the late onset of aGVHD.
Recent discovery of the copy number variation (CNV) in normal individuals has widened our understanding of genomic variation. However, most of the reported CNVs have been identified in Caucasians, ...which may not be directly applicable to people of different ethnicities. To profile CNV in East-Asian population, we screened CNVs in 3578 healthy, unrelated Korean individuals, using the Affymetrix Genome-Wide Human SNP array 5.0. We identified 144 207 CNVs using a pooled data set of 100 randomly chosen Korean females as a reference. The average number of CNVs per genome was 40.3, which is higher than that of CNVs previously reported using lower resolution platforms. The median size of CNVs was 18.9 kb (range 0.2–5406 kb). Copy number losses were 4.7 times more frequent than copy number gains. CNV regions (CNVRs) were defined by merging overlapping CNVs identified in two or more samples. In total, 4003 CNVRs were defined encompassing 241.9 Mb accounting for ∼8% of the human genome. A total of 2077 CNVRs (51.9%) were potentially novel. Known CNVRs were larger and more frequent than novel CNVRs. Sixteen percent of the CNVRs were observed in ≥1% of study subjects and 24% overlapped with the OMIM genes. A total of 476 (11.9%) CNVRs were associated with segmental duplications. CNVS/CNVRs identified in this study will be valuable resources for studying human genome diversity and its association with disease.
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