Analog

摘要： BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

摘要： BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.

摘要： IEEE J.Solid-State Circuits,2019,doi:10.1109/JSSC.2018.2889847Low power is a fundamental requirement in state-ofthe-art IC designs,where lower and scalable supply voltagesare demanded due to the power benefits of digital circuits under near-and sub-threshold supply voltages.

摘要： Background: Diet plays a vital role in managing diabetes. Foods with a low glycemic index provide lower postprandial glucose spikes and induce satiety. The objective of this study was to assess the Glycemic index (GI) without milk and Glycemic response (GR) with milk of two different flavours of a plant-based supplement which is high in protein and fibre, along with a subjective assessment of satiety. Methods: Fifteen overweight/obese subjects aged 18 - 45 years were recruited. After overnight fasting, blood samples were drawn at 5 mins before food consumption (-5), 0, 15, 30, 45, 60, 90 and 120 minutes. Participants underwent 3 days of reference food testing and 1 day of test food in random order with 2 days of wash-out period. The GI was assessed using a validated protocol recognized by FAO/WHO, as well as the guidelines by the International Dietary Carbohydrate Task Force for GI Methodology. The satiety index was measured using the Visual Analog Scale (VAS). The dietary intake of the subjects was measured by 24-hour dietary recall. The Incremental Area Under the Curve (IAUC) was calculated using the trapezoid rule. Results: Both the flavours of the supplement had low GI & GR. The GI and GR of Flavour 1 were 27.3 ± 4.8 & 16.4 ± 2.6 (Mean ± SEM) respectively. For Flavour 2 the GI and GR were 36.7 ± 4.4 & 25.7 ± 2.3 (Mean ± SEM). For Flavour 1, 60% and for flavour 2 66.7% of subjects reported feeling hungry only after 3 hours, showing good satiety. Conclusion: The plant-based high fibre high protein supplement in both flavours showed a low glycemic index and hence may be useful to include in the diets to reduce the postprandial glycemic response and could improve satiety.

摘要： AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.

摘要： Our contention is that reality is actually analog, but at a critical limit, when the Octonian gravity condition kicks in, for a time it is made to appear discrete. This is due to an initial phase transition just at the start of the big bang. Our second consideration is that symmetry breaking models, i.e. the Higgs boson, are in themselves not appropriate or necessary for the formation of particles with mass just before Octonionic gravity which could arise in pre-Planckian physics models without a potential. Finally, the necessity of potentials for pre-Octonionic gravity physics can be circumvented via judicious use of Scherrer k essence physics.

摘要： There are DAC structures available in the literature for radix r = 2, 3, and 4;but how they are arrived at is missing. No general structure is available for any radix r. The aim of the paper is, therefore, to fulfil these gaps. To start with, the design relations are derived for the simplest possible attenuator circuit when connected to a voltage source V and a series resistance R, such that the complete circuit offers the Thevenin resistance R. Spread relations for this attenuator are derived. An example when 3 such attenuators with different attenuation constants are connected in cascade is given. Interestingly, the two attenuators with attenuation factors 1/2 and 1/3 have the same spread of 2. A generalized attenuator is then obtained when N number of identical attenuators are connected in cascade. This is modified to derive a digital to analog converter for any radix r.

摘要： The paper presents a new universal biquadratic filter using single universal voltage conveyor (UVC), two resistors and two capacitors. The offered structure has three inputs and one output and can realise all the five basic biquadratic filters: high-pass (HP), low-pass (LP), band-reject (BR), band-pass (BP) and all-pass (AP) from the same circuit topology. The proposed universal filter also provides following advantageous features, not available simultaneously in any UVC based universal biquadratic filter so far: (i) low active and passive sensitivities, (ii) independent control of natural frequency (ω0) and bandwidth (BW) and (iii) no requirement of any component matching condition and inversion of input signal(s) (as needed in most of the earlier reported structures). The workability of proposed structure has been presented by SPICE (Version 16.5) simulation using 0.18 μm TSMC technology.

摘要： In this work a method called “signal flow graph (SFG)” is presented. A signal-flow graph describes a system by its signal flow by directed and weighted graph;the signals are applied to nodes and functions on edges. The edges of the signal flow graph are small processing units, through which the incoming signals are processed in a certain form. In this case, the result is sent to the outgoing node. The SFG allows a good visual inspection into complex feedback problems. Furthermore such a presentation allows for a clear and unambiguous description of a generating system, for example, a netview. A Signal Flow Graph (SFG) allows a fast and practical network analysis based on a clear data presentation in graphic format of the mathematical linear equations of the circuit. During creation of a SFG the Direct Current-Case (DC-Case) was observed since the correct current and voltage directions was drawn from zero frequency. In addition, the mathematical axioms, which are based on field algebra, are declared. In this work we show you in addition: How we check our SFG whether it is a consistent system or not. A signal flow graph can be verified by generating the identity of the signal flow graph itself, illustrated by the inverse signal flow graph (SFG?1). Two signal flow graphs are always generated from one circuit, so that the signal flow diagram already presented in previous sections corresponds to only half of the solution. The other half of the solution is the so-called identity, which represents the (SFG?1). If these two graphs are superposed with one another, so called 1-edges are created at the node points. In Boolean algebra, these 1-edges are given the value 1, whereas this value can be identified with a zero in the field algebra.

摘要： A universal biquadratic filter using single universal voltage conveyor (UVC), two resistors and two capacitors is presented in this paper. The proposed structure has three inputs and one output and can realize all the five standard biquadratic filters: low-pass (LP), high-pass (HP), band-pass (BP), band-reject (BR) and all-pass (AP) from the same circuit configuration. The presented universal filter offers low active and passive sensitivities. SPICE (Version 16.5) simulation results using 0.18 μm TSMC technology have been included.