With the emergence of large-language models (LLM) and generative AI, which require an enormous amount of model parameters, the required memory bandwidth and capacity for high-end systems is on an ...unprecedented increase. To meet this need, we present an extended version of the high-bandwidth memory-3 (HBM3 DRAM), HBM3E, which achieves a 1280GB/s bandwidth with a cube density of 48GB. New design schemes and features, such as all-around power-through-silicon via (TSV), a 6-phase read-data-strobe (RDQS) scheme, a byte-mapping swap scheme, and a voltage-drift compensator for write data strobe (WDQS), are implemented to achieve extended bandwidth and capacity with enhanced reliability. The overall architecture and specifications, such as bump map footprint, the number of channel and I/Os, and the operation voltage, are identical to the latest HBM3 1, 2; therefore, backward compatibility is provided, avoiding system modification.
Ever since the introduction of high bandwidth memory (HBM DRAM) and its succeeding line-ups, HBM DRAM has been heralded as a prominent solution to tackle the memory wall problem. However, despite ...continual memory advancements the advent of high-end systems, including supercomputers, hyper-scale data centers and machine learning accelerators, are expediting requirements for higher-performance memory solutions. To accommodate the increasing system-level demands, we introduce HBM3 DRAM, which employs multiple new features and design schemes. Techniques such as an on-die ECC engine, internal NN-DFE I/O signaling, TSV auto-calibration, and layout optimization based on machine-learning algorithms are implemented to efficiently control timing skew margins and SI degradation trade-offs. Furthermore, reduced voltage swings allow for improved memory bandwidth, density, power efficiency and reliability.
Two angiostatic fusion proteins (hAE and hEA), differing in tandem connection manners, were constructed from human angiostatin (hAS) and endostatin (hES) proteins. These fusion proteins were then ...evaluated for synergistic antiangiogenic properties. The 65 kDa secreted fusion proteins, expressed in Pichia pastoris, were verified by both mass analysis and Western blotting assay. Luciferase reporter gene assay, using a VEGF promoter, revealed that the angiostatin endostatin fusion protein (hAE), and its corresponding fusion gene delivery on human microvascular endothelial cells (HMEC-1), resulted in a more potent synergistic antiangiogenic effect than the endostatin-angiostatin fusion protein (hEA). These results suggest that the orientation of the fusion genes in hAS and hES might be an important factor in the development of therapeutic proteins.
In this paper, we propose a new scheme to generate region-of-interest (ROI) enhanced depth maps combining one low-resolution depth camera with high-resolution stereoscopic cameras. Basically, the ...hybrid camera system produces four synchronized images at each frame: left and right images from the stereoscopic cameras, a color image and its associated depth map from the depth camera. In the hybrid camera system, after estimating initial depth information for the left image using a stereo matching algorithm, we project depths obtained from the depth camera onto ROI of the left image using three-dimensional (3-D) image warping. Then, the warped depths are linearly interpolated to fill depth holes occurred in ROI. Finally, we merge the ROI depths with background ones extracted from the initial depth information to generate the ROI enhanced depth map. Experimental results show that the proposed depth acquisition system provides more accurate depth information for ROI than previous stereo matching algorithms. Besides, the proposed scheme minimizes inherent problems of the current depth camera, such as limitation of its measuring distance and production of low-resolution depth maps.
The potential benefits of generating and using transgenic cattle range from improvements in agriculture to the production of large quantities of pharmaceutically relevant proteins. Previous studies ...have attempted to produce transgenic cattle and other livestock by pronuclear injection and somatic cell nuclear transfer, but these approaches have been largely ineffective; however, a third approach, lentivirus-mediated transgenesis, has successfully produced transgenic livestock. In this study, we generated transgenic (TG) Korean native cattle using perivitelline space injection of viral vectors, which expressed enhanced green fluorescent protein (EGFP) systemically. Two different types of lentiviral vectors derived from feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) carrying EGFP were injected into the perivitelline space of MII oocytes. EGFP expression at 8-cell stage was significantly higher in the FIV group compared to the HIV group (47.5%±2.2% v.s. 22.9%±2.9%). Eight-cell embryos that expressed EGFP were cultured into blastocysts and then transferred into 40 heifers. Ten heifers were successfully impregnated and delivered 10 healthy calves. All of these calves expressed EGFP as detected by in vivo imaging, PCR and Southern blotting. In addition, we established an EGFP-expressing cell line from TG calves, which was followed by nuclear transfer (NT). Recloned 8-cell embryos also expressed EGFP, and there were no differences in the rates of fusion, cleavage and development between cells derived from TG and non-TG calves, which were subsequently used for NT. These results illustrate that FIV-based lentiviruses are useful for the production of TG cattle. Moreover, our established EGFP cell line can be used for additional studies that involve induced pluripotent stem cells.
Valproic acid (2‐propylpentanoic acid, VPA) has been widely used as an anticonvulsant drug and is a choice drug for seizure treatment. VPA is also used as a short‐chain fatty acid HDAC inhibitor that ...affects proliferation and differentiation and induces cell apoptosis in both solid and haematologic malignancies. Here, we observed that VPA treatment inhibited HDAC1/2 activity and induced autophagy in gastric cancer cells, leading to apoptosis. VPA‐induced apoptosis occurred through inhibition of the HDAC1/PTEN/Akt signalling pathway and involved alterations in Bcl‐2 and Beclin‐1. The antitumour effects of VPA were verified in vivo using SGC‐7901 xenograft models. Moreover, we evaluated the expression of HDAC1/2 in gastric cancer patient samples and revealed a positive correlation between HDAC1/2 overexpression and poor prognosis. These findings indicate that VPA may serve as a potential therapeutic agent for gastric cancer and that HDAC1/2 might be a promising therapeutic biomarker for the disease.
Valproic acid (VPA) is used as a short‐chain fatty acid HDAC inhibitor. We demonstrated that VPA inhibited HDAC1/2 activity and induced autophagy in gastric cancer though HDAC1/PTEN/Akt pathway inactivation. Moreover, we revealed a positive correlation between HDAC1/2 overexpression and poor prognosis in gastric cancer patients. These results suggest that VPA might be a potential agent for gastric cancer treatment and that HDAC1/2 may serve as a therapeutic target for gastric cancer.
Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched ...the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as ...endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)‐containing plasmalogens, expression of glyceronephosphate O‐acyltransferase (Gnpat; the rate‐limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of FC in the liver. Cyclodextrin‐induced depletion of FC transactivated Δ‐6 desaturase by increasing sterol regulatory element‐binding protein 2 expression in cultured hepatocytes. DHA, the major product of Δ‐6 desaturase activation, activated GNPAT, thereby explaining the association between high hepatic FC and decreased Gnpat expression. Gnpat small interfering RNA treatment significantly decreased peroxisome proliferator‐activated receptor α (Pparα) expression in cultured hepatocytes. In addition to GNPAT, DHA activated PPARα and increased expression of Pparα and its target genes, suggesting that DHA in the DHA‐containing plasmalogens contributed to activation of PPARα. Accordingly, administration of the plasmalogen precursor, alkyl glycerol (AG), prevented hepatic steatosis and NASH through a PPARα‐dependent increase in fatty acid oxidation. Gnpat+/– mice were more susceptible to hepatic lipid accumulation and less responsive to the preventive effect of fluvastatin on NASH development, suggesting that endogenous plasmalogens prevent hepatic steatosis and NASH. Conclusion: Increased hepatic FC in animals with NASH decreased plasmalogens, thereby sensitizing animals to hepatocyte injury and NASH. Our findings uncover a novel link between hepatic FC and plasmalogen homeostasis through GNPAT regulation. Further study of AG or other agents that increase hepatic plasmalogen levels may identify novel therapeutic strategies against NASH. (Hepatology 2017;66:416–431).
Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. However, little is known about its active ingredients and the molecular mechanisms underlying its ...anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin, from ginseng. Gintonin, the glycolipoprotein fraction of ginseng, contains LPAs, mainly LPA C18 : 2 with other minor lysophospholipid components. A line of evidence showed that serum autotaxin (ATX) activity and level are significantly elevated in human AD patients compared to those in normal controls, which indicates that ATX may be involved in human AD. In a previous study, we demonstrated that gintonin exerted anti-inflammatory effects via inhibition of microglial activation and proinflammatory cytokine production by immune cells and that it strongly inhibited ATX activity. In this study, we investigated whether oral administration of the gintonin-enriched fraction (GEF) could ameliorate the symptoms of 2,4-dinitrofluorobenzene (DNFB)-induced AD in NC/Nga mice. We found that oral administration of GEF to DNFB-induced AD mice for 2 weeks reduced ear swelling and AD skin index. In addition, oral administration of GEF reduced the serum levels of immunoglobulin E, histamine, interleukin-4, and interferon-γ. Histological examination showed that oral administration of GEF attenuated skin inflammation and significantly reduced eosinophil and mast cell infiltration into the skin. Moreover, oral administration of GEF not only decreased serum ATX level but also reduced serum ATX activity. The present study shows that the anti-AD effects of ginseng might be attributed to GEF-induced anti-inflammatory activity and ATX regulation.
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