Robots are versatile machines that can perform complex manipulation operations. Recent advances in industrial robotics make robots useful in a wide variety of manufacturing processes. Several recent ...efforts have demonstrated how robots can be used in additive manufacturing (AM) processes. This paper surveys the work focused on expanding the functional capabilities of AM processes using robots. We identify the following main capabilities realized by performing AM using robots: (1) multi-directional fabrication, (2) conformal deposition, (3) assembling prefabricated components in AM, (4) supportless AM, and (5) large-scale AM. We classify the recent literature in this area in terms of mechanisms, kinematic degrees of freedom (DOF) of the system, types of AM process, and materials. Finally, we discuss the limitations of the current work and the opportunities for future research in this area.
Increased levels of hypoxia and hypoxia‐inducible factor 1α (HIF‐1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged antiangiogenic therapy of tumors not only ...delays tumor growth but may also increase hypoxia and HIF‐1α activity. In our recent clinical trial, treatment with the vascular endothelial growth factor A (VEGF‐A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene Set Enrichment Analysis of microarrays from pretreatment biopsies found that the Gene Ontology category “Response to hypoxia” was upregulated in poor responders and that the hierarchical clustering based on 140 hypoxia‐responsive genes reliably separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF‐1α binding to DNA at low metronomic doses. In four sarcoma cell lines, HIF‐1α shRNA or Dox at low concentrations blocked HIF‐1α induction of VEGF‐A by 84–97% and carbonic anhydrase 9 by 83–93%. HT1080 sarcoma xenografts had increased hypoxia and/or HIF‐1α activity with increasing tumor size and with anti‐VEGF receptor antibody (DC101) treatment. Combining DC101 with HIF‐1α shRNA or metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, at least in part via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF‐1α target genes that may promote resistance to antiangiogenic and other therapies. HIF‐1α inhibition blocks this evasive resistance and augments destruction of the tumor vasculature.
What's new?
Despite their initial promise, anti‐angiogenic therapies have been a disappointment in the clinic. One reason is that solid tumors often become resistant to these drugs. Tumors that respond poorly to this type of therapy have increased activation of the hypoxia‐induced transcription factor HIF‐1α which can enhance tumor survival and progression. In this study, the authors report that this evasive resistance can be overcome by adding low‐dose doxorubicin or shRNA to inhibit HIF‐1α activity. They are thus developing a clinical trial combining the angiogenesis inhibitor bevacizumab with metronomic doxorubicin in sarcoma patients.
To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie ...trimodality therapy) for soft-tissue sarcoma.
Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines.
In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm(3) within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm(3) for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays.
Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature.
In May 2019, UAV photogrammetry using drones (unmanned aircraft) was conducted to investigate the spatial distribution characteristics of the seagrass habitat in Wan Island. Wan Is. sea was divided ...into 3 geographical areas (Site A, B, C) by referring to the seagrass distribution identified by the National Coastal seagrass forest precision survey (Ministry of Oceans and Fisheries, 2015), and contour lines were extracted from grid depth data. In addition, a 3-D benthic topographic map using DTM (Digital Terrain Model) was created to understand the characteristics and slope of the benthic topographic map. Through the analysis of the seagrass distribution results and the water depth results, it was confirmed that the boundary between the seagrass distribution in the outer and coastal areas converges to different water depth limits (within 10 m, and within 5 m), which is estimated to be based on the characteristics of the outer sea area. As a result of the analysis of the benthic topography, it was confirmed that the slope of the well-covered distribution was relatively gentle below 0.2~0.8 degrees, and the well-covered distribution was limited to the vicinity of the boundary where the slope changed rapidly. As a result of comparing the area of the seagrass distribution survey in 2015 and 2019, it was confirmed that the area was 238.4 ha and 1,070.9 ha, respectively, which was 4.5 times more widerly when performing Drone survey than diving survey. In order to understand the surrounding environment of the seagrass distribution site, satellite image data and license fishing ground information map at the time of drone shooting (May 2019) were checked. As a result, seaweed (Kelp, Sea mustard seaweed, Seaweed, Seaweed fulvescens, etc.) and shellfish (Abalone) were densely distributed, and most of the facilities except for Seaweed fulvescens farms were separated from their habitat. Drone survey confirmed Zostera marina, Zostera caulescens, and Zostera japonica in Wan Is., but no Phyllospadix iwatensis and Halophila nipponica were identified in 2015. It was confirmed that there was a limit to classifying the types of vegetation due to the characteristics of Phyllospadix iwatensis attached to the rock substrate, and in the case of Halophila nipponica with short leaves of 2 to 3 cm, they were not exposed to the water even at low tide, so there was a limit to detection using drones. These research results are expected to be useful data for grasping the characteristics of a wide range of seagrass habitats in other seas in the future.
Egr4 is expressed in primary and secondary spermatocytes in adult mouse testes and has a crucial role in regulating germ cell maturation. The functional loss of Egr4 blocks spermatogenesis, ...significantly reducing the number of spermatozoa that are produced. In this study, we examined whether EGR4 variants are present in Korean men with impaired spermatogenesis.
A total 170 Korean men with impaired spermatogenesis and 272 normal controls were screened. The coding regions including exon-intron boundaries of EGR4 were sequenced by PCR-direct sequencing method.
We identified eight sequence variations in the coding region and 3'-UTR regions of the EGR4 gene. Four were nonsynonymous variants (rs771189047, rs561568849, rs763487015, and rs546250227), three were synonymous variants (rs115948271, rs528939702, and rs7558708), and one variant (rs2229294) was localized in the 3'-UTR. Three nonsynonymous variants c.65_66InsG (p. Cys23Leufs*37), c.236C > T (p. Pro79Leu), c.1294G > T (p. Val432Leu) and one synonymous variant c.1230G > A (p. Thr410) were not detected in controls. To evaluate the pathogenic effects of nonsynonymous variants, we used seven prediction methods. The c.214C > A (p. Arg72Ser) and c.236C > T (p. Pro79Leu) variants were predicted as "damaging" by SIFT and SNAP
. The c.65_66insG (p. Cys23Leufs*37) variants were predicted as "disease causing" by Mutation Taster, SNPs &GO and SNAP
. The c.867C > G (p. Leu289) variants were predicted as "disease causing" only by Mutation Taster.
To date, this study is the first to screen the EGR4 gene in relation to male infertility. However, our findings did not clearly explain how nonsynonymous EGR4 variations affect spermatogenesis. Therefore, further studies are required to validate the functional impact of EGR4 variations on spermatogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, we investigated the relationship between unsaturated fatty acids influencing beef flavor and four types of SNPs (c.280A>G, c.388G>A, c.408G>C and c.456A>G) located at exon 2, 3 and 4 ...of the FABP4 gene, which is a fatty acid binding protein 4 in Korean cattle (n = 513). When analyzing the relationship between single genotype, fatty acids and carcass trait, individuals of GG, GG, CC and GG genotypes that are homozygotes, had a higher content of unsaturated fatty acids and marbling scores than other genotypes (p<0.05). Then, haplotype block showed strong significant relationships not only with unsaturated fatty acids (54.73%), but also with marbling scores (5.82) in ht1×ht1 group (p<0.05). This ht1×ht1 group showed significant differences with unsaturated fatty acids and marbling scores that affected beef flavor in Korean cattle. Therefore, it can be inferred that the ht1×ht1 types might be valuable new markers for use in the improvement of Korean cattle.
Fat quality is determined by the composition of fatty acids. Genetic relationships between this composition and single nucleotide polymorphisms (SNPs) in the stearoyl-CoA desaturase1 (SCD1) gene were ...examined using 513 Korean native cattle. Single and epistatic effects of 7 SNP genetic variations were investigated, and the multifactor dimensionality reduction (MDR) method was used to investigate gene interactions in terms of oleic acid (C18:1), mono-unsaturated fatty acids (MUFAs) and marbling score (MS). The g.6850+77 A>G and g.14047 C>T SNP interactions were identified as the statistically optimal combination (C18:1, MUFAs and MS permutation p-values were 0.000, 0.000 and 0.001 respectively) of two-way gene interactions. The interaction effects of g.6850+77 A>G, g.10213 T>C and g.14047 C>T reflected the highest training-balanced accuracy (63.76%, 64.70% and 61.85% respectively) and was better than the individual effects for C18:1, MUFAs and MS. In addition, the superior genotype groups were AATTCC, AGTTCC, GGTCCC, AGTCCT, GGCCCT and AGCCTT. These results suggest that the selected SNP combination of the SCD1 gene and superior genotype groups can provide useful inferences for the improvement of the fatty acid composition in Korean native cattle.
The thyroid hormone responsive protein (THRSP) gene is a functional gene that can be used to indicate the fatty acid compositions. This study investigates the relationships of exonic single ...nucleotide polymorphisms (SNPs) in the THRSP gene and fatty acid composition of muscle fat and marbling score in the 612 Korean cattle. The relationships between fatty acid composition and eight SNPs in the THRSP gene (g.78 G>A, g.173 C>T, g.184 C>T, g.190 C>A, g.194 C>T, g.277 C>G, g.283 T>G and g.290 T>G) were investigated, and according to the results, two SNPs (g.78 G>A and g.184 C>T) in exon 1 were associated with fatty acid composition. The GG and CC genotypes of g.78 G>A and g.184 C>T had higher unsaturated fatty acid (UFA) and monounsaturated fatty acid (MUFA) content (p<0.05). In addition, the ht1*ht1 group (Val/Ala haplotype) in a linkage disequilibrium increased MUFAs and marbling scores for carcass traits (p<0.05). As a result, g.78 G>A and g.184 C>T had significantly relationships with UFAs and MUFAs. Two SNPs in the THRSP gene affected fatty acid composition, suggesting that GG and CC genotypes and the ht1*ht1 group (Val/Ala haplotype) can be markers to genetically improve the quality and flavor of beef.
Objective We aimed to determine whether the extension of ablation could influence the ablation outcome for ventricular tachycardia (VT)/premature ventricular contractions (PVCs) from the right ...ventricular outflow tract (RVOT).
Methods and results The radiofrequency catheter ablation results of 33 VT/6 frequent PVCs from the RVOT were analysed. The ablation extension was divided into 3 categories from the final successful ablation point with the earliest activation: (I) focal ablation (15 cases); ablation at 1 or 2 points; (II) focal with extended ablation (12 cases); focal and surrounding area ablation (maximum ≤1 cm) after elimination of clinical VT/PVCs; and (III) broad ablation (12 cases); continued broad ablation (maximum >1 cm) after elimination of clinical VT/PVCs. Acute termination was defined as the complete elimination and non-inducibility of clinical VT/PVCs during the procedure. For the mean follow-up of 12.8 months, the recurrence rate was not significantly different among the groups (P = 0.49). The mean procedure time was longer in group II, but ablation times and complication rates were not different among the groups. When acute termination was achieved, the overall recurrence rate was 7.6%. However, when confirming absence of the clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure, the recurrence rate was 2.7%.
Conclusions Ablation extension did not affect ablation outcome of VT/PVCs from the RVOT. Confirmation of absence of clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure could guarantee long-term success.
전기 고생대 태백산분지의 분지 진화 권이균(Yi Kyun Kwon); 권유진(Yoo Jin Kwon); 여정민(Jung Min Yeo) ...
자원환경지질,
10/2019, Letnik:
52, Številka:
5
Journal Article
Odprti dostop
This study reconstructed the paleoenvironments and paleogeography of the Taebaeksan Basin, through a review of the previous researches on sedimentology, paleontology and stratigraphy. This study also ...carried out a sequence stratigraphic analysis on regional tectonism and sea-level fluctuations on the basin during the Early Paleozoic. The basin broadly occur in the Taebaek, Yeongweol-Jecheon, Jeongseon-Pyeongchang, and Mungyeong areas, Gangwon province, South Korea. The basin-fills are composed mainly of mixed carbonates and siliciclastics, divided into the Taebaek, Yeongweol, Yongtan, Pyeongchang and Mungyeong groups according to lithologies and stratigraphic characteristics. Recently, there are a lot of studies on the provenance and depositional ages of the siliciclastic sequences of the basin. The detrital sediments of the basin would be derived from two separated provenances of the core-Gondwana and Sino-Korean cratons. In the Early Cambrian, the Taebaek and Jeongseon-Pyeongchang platforms have most likely received detrital sediments from the provenance of the Sino-Korean craton. On the other hand, the detrital sediments of the Yeongweol-Jecheon platform was probably sourced by those of the core-Gondwana craton. This separation of provenance can be interpreted as the result of the paleogeographic and paleotopographic separation of the Yeongweol-Jecheon platform from the Taebaek and Jeongseon-Pyeongchang platforms. The analyses on detrital zircons additionally reveal that the separation of provenance was ceased by the eustatic rise of sea-level during the Middle Cambrian, and the detrital sediments of the Taebaeksan Basin were entirely supplied from those of the core-Gondwana craton. During that period, sediment supply from the Sino-Korean craton would be restricted due to inundation of the provenance area of the craton. On the other hand, the Jeongseon-Pyeongchang platform sequences show the unconformable relationship between the Early Cambrian siliciclastic and the Early Ordovician carbonate strata. It is indicative of presence of regional uplift movements around the platform which would be to the extent offset of the effects of the Middle to Late Cambrian eustatic sealevel rise. These movements expanded and were reinforced across the basin in the latest Cambrian and earliest Ordovician. After the earliest Ordovician, the basin was tectonically stabilized, and the shallow marine carbonate environments were developed on the whole-platform by the Early Ordovician global eustatic sea-level rise, forming very thick carbonate strata in the basin. In the Late Ordovician, the Early Paleozoic sedimentation on the basin was terminated by the large-scale tectonic uplift across the Sino-Korean platform including the Taebaeksan Basin. 본 연구는 최근 수행된 퇴적층서학 및 고생물학적 연구결과를 종합하고, 새롭게 분석된 자료를 보강하여, 전기 고생대 태백산분지의 고환경과 고지리를 복원하였다. 또한 순차층서학적 방법을 사용하여 조구조적 운동과 해수면 변동을 추적하여 종합적인 분지해석을 수행하였다. 태백산분지는 태백, 정선-평창, 영월-제천, 문경 지역에 넓게 분포하고 있으며, 암상 및 층서 특성에 따라 태백, 영월, 용탄, 평창, 문경 층군으로 구분되어 조사 및 연구가 진행되어 왔다. 태백산분지의 퇴적체는 탄산염암과 규산쇄설성 퇴적암이 혼합되어 있는데, 최근 쇄설성 퇴적물의 기원과 퇴적 연대에 대한 연구가 집중적으로 이루어졌다. 태백산분지에 공급되는 쇄설성 퇴적물의 근원지는 크게 곤드와나지괴와 한중지괴 기원지로 나누어진다. 태백산분지의 형성 초기에 태백대지와 정선-평창대지는 주로 한중지괴 기원지로부터 퇴적물을 공급 받았으며, 영월-제천 대지는 지리적 혹은 지형적 분리에 의해 한중지괴의 영향이 차단되고, 주로 곤드와나지괴 기원지로부터 퇴적층을 공급받았다. 쇄설성 저어콘 분석 결과는 중기 캠브리아 시기의 전 지구적 해수면 상승으로 인해 태백산분지 전체적으로 곤드와나지괴 기원의 퇴적물이 공급되었으며, 한중지괴 기원의 퇴적물은 공급이 멈추었음을 보여주고 있다. 한편, 태백산분지의 북쪽에 분포하는 정선-평창 대지의 퇴적체는 전기 캠브리아기와 오르도비스기 지층사이에 부정합 관계를 보여주고 있는데, 이것은 중기-후기 캠브리아 시기에 전 지구적 해수면 상승효과를 상쇄할 규모의 지역적 융기 운동이 정선-평창 대지 인근에서 존재했음을 보여준다. 이러한 융기운동은 최후기 캠브리아기와 최전기 오르도비스기에 태백산 분지 전역으로 확대되었다. 최전기 오르도비스기 이후에 태백산 분지는 조구조적으로 안정화되었고, 분지 전체적으로 해수면이 상승하면서 천해 탄산염 퇴적환경이 조성되어 두꺼운 탄산염암이 형성되었다. 전기 고생대 태백산분지의 퇴적작용은 후기 오르도비스기 동안 태백산분지와 한중지괴 전역에서 발생한 융기운동에 의해 종료되었다.
PDF
