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关键词： Early-onset   Alzheimer's disease   [F-18]flortaucipir   Tau pathology   Cerebral blood flow   Cognition  

摘要： Purpose Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [F-18]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD. Methods Seventy-nine amyloid-positive individuals with a clinical diagnosis of AD (EOAD: n = 35, age-at-PET = 59 +/- 5, MMSE = 23 +/- 4;LOAD: n = 44, age-at-PET = 71 +/- 5, MMSE = 23 +/- 4) underwent a 130-min dynamic [F-18]flortaucipir PET scan and extensive neuropsychological assessment. We extracted binding potentials (BPND) and R-1 (proxy of rCBF) from parametric images using receptor parametric mapping, in medial and lateral temporal, parietal, occipital, and frontal regions-of-interest and used nine neuropsychological tests covering memory, attention, language, and executive functioning. We first examined differences between EOAD and LOAD in BPND or R-1 using ANOVA (region-of-interest analysis) and voxel-wise contrasts. Next, we performed linear regression models to test for potential interaction effects between age-at-onset and BPND/R-1 on cognition. Results Both region-of-interest and voxel-wise contrasts showed higher [F-18]flortaucipir BPND values across all neocortical regions in EOAD. By contrast, LOAD patients had lower R-1 values (indicative of more reduced rCBF) in medial temporal regions. For both tau and flow in lateral temporal, and occipitoparietal regions, associations with cognitive impairment were stronger in EOAD than in LOAD (EOAD BPND - 0.76 <= st beta <= - 0.48 vs LOAD - 0.18 <= st beta <= - 0.02;EOAD R-1 0.37 <= st beta <= 0.84 vs LOAD - 0.25 <= st beta <= 0.16). Conclusions Compared to LOAD, the degree of lateral temporal and occipitoparietal tau pathology and relative cerebral blood-flow is more strongly associated with cognition in EOAD.

关键词： common-mode feedback (CMFB)   differential difference amplifier (DDA)   operational transconductance amplifier (OTA)  

摘要： This paper proposes a new approach to improve loop stability in a typical common-mode feedback (CMFB) circuit of a differential operational transconductance amplifier (OTA). In this paper, a differential difference amplifier (DDA) with a current mirror load is employed as a CMFB circuit. The new approach is based on using two series diode-connected transistors operating in subthreshold region in parallel with current mirror load. The proposed approach provides a reliable good function with no reduction in the OTA performance and dynamic operation of CMFB loop. The proposed scheme attains necessary high gain and large bandwidth with required phase margin for CMFB circuit. The proposed CMFB circuit is employed in a typical OTA structure. The post-layout simulation results in TSMC 130-nm CMOS technology show that the proposed approach leads to a better phase margin of 80 degrees, a high unity gain bandwidth of 800 MHz, and a loop gain of 27 dB for the CMFB circuit.

关键词： gold micro shunt   long-term follow-up   refractory glaucoma   supraciliary shunt  

摘要： Purpose To evaluate the 10-year follow-up efficacy and safety of gold micro shunt (GMS) in patients with refractory glaucoma, and the potential risk factors for failure. Methods Retrospective data analyses based on medical records from 55 patients who underwent GMS implant for refractory glaucoma between March 2007 and April 2008. The primary outcome measure was the cumulative probability of success defined as intraocular pressure (IOP) below 21 mmHg together with a 33% lowering of the baseline IOP with (qualified) or without (complete) topical medications, no reoperation for glaucoma or loss of light perception. Results Mean IOP 10 years after the GMS implantation was 21.6 +/- 5.1 mmHg with 2.7 +/- 0.7 drugs. Qualified success was achieved in 8/55 patients (14.5%) with a mean of 2.9 +/- 0.8 drugs at 5 years and in 2/55 patients (3.6%) with a mean of 2.7 +/- 1.0 drugs at 10 years. None of the patients reached complete success at five years from surgery. The cumulative probability of complete success was 14%, 9% and 0% at 1, 2 and 5 years, respectively, and 72%, 67%, 36% and 3.6% at 1, 2, 5 and 10 years, respectively, for qualified success criterion. Baseline IOP for complete success, number of baseline medication for qualified success and age at the time of GMS implantation for both criteria were risk factors significantly associated with failure. Conclusion A very low long-term survival rate of GMS in refractory glaucoma was found. Most patients did not reach the IOP success criteria of the study, even with the re-introduction of medications, leading to the need for further surgical procedures.

关键词： Catharanthus roseus   Idioblast cell   Laticifer cell   Monoterpenoid indole alkaloid   Serpentine   Specialized metabolism  

摘要： Bioactive specialized (secondary) metabolites are indispensable for plant development or adjustment to their surrounding environment. In many plants, these specialized metabolites are accumulated in specifically differentiated cells. Catharanthus roseus is a well-known medicinal plant known for producing many kinds of monoterpenoid indole alkaloids (MIAs). C. roseus has two types of specifically differentiated cells accumulating MIAs, so-called idioblast cells and laticifer cells. In this study, we compared each of the cells as they changed during seedling growth, and found that the fluorescent metabolites accumulated in these cells were differentially regulated. Analysis of fluorescent compounds revealed that the fluorescence observed in these cells was emitted from the compound serpentine. Further, we found that the serpentine content of leaves increased as leaves grew. Our findings suggest that idioblast cells and laticifer cells have different biological roles in MIA biosynthesis and its regulation.

关键词： Tick cell lines   Tick-derived promoters   Transfection   Luciferase assay  

摘要： The transfection of plasmids into cell lines for the transient expression of exogenous proteins is a fundamental method for characterizing their functions, cellular localization and interactions. Currently, only a few reports on tick transfection systems and expression plasmids specifically constructed for tick cell lines have been published. In this study, the transcriptome of the tick cell line IDE8 was analyzed to screen for highly-expressed genes. The upstream sequences of these genes were selected as possible tick-derived promoters, and their promoter activity was evaluated using a luciferase assay. Four IDE8-derived sequences with promoter activity were identified, and the promoter activities of three common mammalian promoters, CMV, PGK and CAG, were studied and compared in the IDE8 and IRE/CTVM19 tick cell lines. In the two tick cell lines, the efficiency of the CAG promoter was considerably higher than that of CMV, PGK and the four newly-identified tick promoters. Additionally, time course experiments revealed that the protein expression driven by mammalian promoters reached peak levels on day 3, while the protein expression driven by our constructed tick-derived promoters reached peak levels on day 2 in tick cells. By comparing the transfection efficiency of three transfection reagents with different mechanisms in tick cell lines, we identified Effectene (with Enhancer, Qiagen) as the most effective reagent for tick cells. The findings of this study suggested that there are differences between tick and mammalian cell lines in their response to the transfection system. These findings will contribute to future studies on topics including tick protein function, tick genetic modification and tick-host-pathogen interactions.

关键词： diagnostic tests   network meta-analysis   prion diseases   sensitivity   specificity  

摘要： Background: There are no systematic reviews of cerebrospinal fluid and blood biomarkers for sporadic Creutzfeldt-Jakob disease (sCJD) in specialized care settings that compare diagnostic accuracies in a network meta-analysis (NMA). Methods: We searched Medline, Embase, and Cochrane Library for diagnostic studies of sCJD biomarkers. Studies had to use established diagnostic criteria for sCJD and for diseases in the non-CJD groups, which had to represent a consecutive population of patients suspected as a CJD case, as reference standard. Risk of bias was assessed with QUADAS-2. We conducted individual biomarker meta-analyses with generalized bivariate models. To investigate heterogeneity, we performed subgroup analyses based on QUADAS-2 quality and clinical criteria. For the NMA, we applied a Bayesian beta-binomial ANOVA model. The study protocol was registered at PROSPERO (CRD42019118830). Results: Of 2976 publications screened, we included 16 studies, which investigated 14-3-3 beta (n = 13), 14-3-3 gamma (n = 3), neurofilament light chain (NfL, n = 1), neuron-specific enolase (n = 1), p-tau181/t-tau ratio (n = 2), RT-QuIC (n = 7), S100B (n = 3), t-tau (n = 12), and t-tau/A beta 42 ratio (n = 1). Excluded diagnostic studies had strong limitations in study design. In the NMA, RT-QuIC (0.91;95% CI [0.83, 0.95]) and NfL (0.93 [0.78, 0.99]) were the most sensitive biomarkers for the diagnosis of definite, probable, and possible sCJD cases. RT-QuIC was the most specific biomarker (0.97 [0.89, 1.00]). Heterogeneity in accuracy estimates was high between studies. Conclusions: We identified RT-QuIC as the most accurate biomarker, partially confirming currently applied diagnostic criteria. The shortcomings identified in many diagnostic studies for sCJD biomarkers need to be addressed in future studies.

关键词： Inrush Current   Differential Protection   Power Transformer  

摘要： Power transformer differential protection may confront mal-functioning in authentic discrimination between inrush and internal faults. To tackle the latter mal-functioning, a new two-stages algorithm based on phase content of the current signal of the current transformers (CTs) is put forward. The proposed algorithm is designed based on the fact that the fundamental phase angle of a fault signal ideally remains constant during the fault. However, during inrush cases, the phase angle varies. Also, during the internal fault, the phase angles of the current signals of CTs are in phase while during the external fault, the phase angles of the current signals of CTs are 180 degrees out of phase. In the first stage, the proposed algorithm calculates the fundamental phase angles of the current signals of the CTs using sub-cycle modified recursive least squares (MRLS). Afterward, normalized mean residue (NMR) is employed to measure distance between the estimated phase angles of the CT's currents. MRLS and NMR algorithms require limited samples (i.e. 10 and 5 samples respectively) for executing their calculations. Performance evaluation with simulated and experimental recorded current signals shows the ability of the proposed method in discrimination of the internal faults from inrush and external fault currents.

关键词： finite-difference method   heat equation   mixed-integer programming   optimal control   partial differential equations  

摘要： Mixed-integer optimal control problems governed by partial differential equations (MIPDECOs) are powerful modeling tools but also challenging in terms of theory and computation. We propose a highly efficient state elimination approach for MIPDECOs that are governed by partial differential equations that have the structure of an abstract ordinary differential equation in function space. This allows us to avoid repeated calculations of the states for all time steps, and our approach is applied only once before starting the optimization. The presentation of theoretical results is complemented by numerical experiments.

关键词： Differential somatic cell count   Milk coagulation properties   Milk quality  

摘要： This study aimed to investigate the effect of interaction between total (SCC) and differential somatic cell count (DSCC) on milk yield, composition and coagulation traits from individual dairy cows. A total of 159 224 test-day records (daily milk yield, composition and coagulation traits) have been collected during a period of 14 months from 12 849 Holstein-Friesian and 9275 Simmental cows farmed in 223 herds. The interaction between somatic cell traits was highly significant for almost all the evaluated traits. This study showed that the combined use of SCC and DSCC can be employed for assessing the performances of dairy cows and for monitoring the improvement of milk quality.

关键词： urinary bladder neoplasms   pathology   recurrence.  

摘要： MP59-11