The three-dimensional (3D) cross-point array architecture is attractive for future ultra-high-density nonvolatile memory application. A bit-cost-effective technology path toward the 3D integration ...that requires only one critical lithography step or mask for reducing the bit-cost is demonstrated in this work. A double-layer HfOx-based vertical resistive switching random access memory (RRAM) is fabricated and characterized. The HfOx thin film is deposited at the sidewall of the predefined trench by atomic layer deposition, forming a vertical memory structure. Electrode/oxide interface engineering with a TiON interfacial layer results in nonlinear I–V suitable for the selectorless array. The fabricated HfOx vertical RRAM shows excellent performances such as reset current (<50 μA), switching speed (<100 ns), switching endurance (>108 cycles), read disturbance immunity (>109 cycles), and data retention time (>105 s @ 125 °C).
Giant Piezoelectricity on Si for Hyperactive MEMS Baek, S. H.; Park, J.; Kim, D. M. ...
Science (American Association for the Advancement of Science),
11/2011, Letnik:
334, Številka:
6058
Journal Article
Recenzirano
Microelectromechanical systems (MEMS) incorporating active piezoelectric layers offer integrated actuation, sensing, and transduction. The broad implementation of such active MEMS has long been ...constrained by the inability to integrate materials with giant piezoelectric response, such as Pb(MG 1/3 Nb 2/3 )O₃-PbTiO₃ (PMN-PT). We synthesized high-quality PMN-PT epitaxial thin films on vicinal (001) Si wafers with the use of an epitaxial (001) SrTiO₃ template layer with superior piezoelectric coefficients (e 31,f = -27 ± 3 coulombs per square meter) and figures of merit for piezoelectric energy-harvesting systems. We have incorporated these heterostructures into microcantilevers that are actuated with extremely low drive voltage due to thin-film piezoelectric properties that rival bulk PMN-PT single crystals. These epitaxial heterostructures exhibit very large electromechanical coupling for ultrasound medical imaging, microfluidic control, mechanical sensing, and energy harvesting.
Huntington's disease is caused by an expanded CAG repeat in the gene encoding huntingtin (HTT), resulting in loss of striatal and cortical neurons. Given that the gene product is widely expressed, it ...remains unclear why neurons are selectively targeted. Here we show the relationship between synaptic and extrasynaptic activity, inclusion formation of mutant huntingtin protein (mtHtt) and neuronal survival. Synaptic N-methyl-D-aspartate-type glutamate receptor (NMDAR) activity induces mtHtt inclusions via a T complex-1 (TCP-1) ring complex (TRiC)-dependent mechanism, rendering neurons more resistant to mtHtt-mediated cell death. In contrast, stimulation of extrasynaptic NMDARs increases the vulnerability of mtHtt-containing neurons to cell death by impairing the neuroprotective cyclic AMP response element-binding protein (CREB)-peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) cascade and increasing the level of the small guanine nucleotide-binding protein Rhes, which is known to sumoylate and disaggregate mtHtt. Treatment of transgenic mice expressing a yeast artificial chromosome containing 128 CAG repeats (YAC128) with low-dose memantine blocks extrasynaptic (but not synaptic) NMDARs and ameliorates neuropathological and behavioral manifestations. By contrast, high-dose memantine, which blocks both extrasynaptic and synaptic NMDAR activity, decreases neuronal inclusions and worsens these outcomes. Our findings offer a rational therapeutic approach for protecting susceptible neurons in Huntington's disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
There is significant interest in understanding the pathophysiology of Obsessive-Compulsive Disorder (OCD) using resting-state fMRI (rsfMRI). Previous studies acknowledge abnormalities within and ...beyond the fronto-striato-limbic circuit in OCD that require further clarifications. However, limited information could be inferred from the conventional way of investigating the functional connectivity differences between OCD and healthy controls. Here, we identified altered brain organization in patients with OCD by applying individual-based approaches to maximize the identification of underlying network-based features specific to the OCD group. rsfMRI of 20 patients with OCD and 22 controls were preprocessed, and individual-fMRI-subspace was derived for each subject within each group. We evaluated group differences in functional connectivity using individual-fMRI-subspace and established its advantage over conventional-fMRI methodology. We applied prediction-based approaches to highlight the group differences by evaluating the differences in functional connections that predicted the clinical scores (namely, the Obsessive-Compulsive Inventory-Revised (OCI-R) and Hamilton Anxiety Rating Scale). Then, we explored the brain network organization of both groups by estimating the subject-specific communities within each group. Lastly, we evaluated associations between the inter-individual variation of nodes in the communities to clinical measures using linear regression. Functional connectivity analysis using individual-fMRI-subspace detected 83 connections that were different between OCD and control groups, compared to none found using conventional-fMRI methodology. Connectome-based prediction analysis did not show significant overlap between the two groups in the functional connections that predicted the clinical scores. This suggests that the functional architecture in patients with OCD may be different compared to controls. Seven communities were found in both groups. Interestingly, within the OCD group but not controls, we observed functional connectivity between cerebellar and visual regions, and lack of connectivity between striato-limbic and frontal areas. Inter-individual variations in the community-size of these two communities were also associated with the OCI-R score (p < .005). Due to our small sample size, we further validated our results by (i) accounting for head motion, (ii) applying global signal regression (GSR) in data processing, and (iii) using an alternate atlas for parcellation. While the main results were consistently observed with accounting for head motion and using another atlas, the key findings were not reproduced with GSR application. The study demonstrated the existence of disconnectedness in fronto-striato-limbic community and connectedness between cerebellar and visual areas in OCD patients, which was also related to the clinical symptomatology of OCD.
At low temperatures, proteins exist in a glassy state, a state that has no conformational flexibility and shows no biological functions. In a hydrated protein, at temperatures ≳220 K, this ...flexibility is restored, and the protein is able to sample more conformational substates, thus becoming biologically functional. This "dynamical" transition of protein is believed to be triggered by its strong coupling with the hydration water, which also shows a similar dynamic transition. Here we demonstrate experimentally that this sudden switch in dynamic behavior of the hydration water on lysozyme occurs precisely at 220 K and can be described as a fragile-to-strong dynamic crossover. At the fragile-to-strong dynamic crossover, the structure of hydration water makes a transition from predominantly high-density (more fluid state) to lowdensity (less fluid state) forms derived from the existence of the second critical point at an elevated pressure.
The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies ...targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.
White muscle concentrations of As, Cd, Cu, Fe, Se, and Zn were investigated in Atlantic- and Indian-bigeye tuna (BET) (Thunnus obesus) from 6 regions. As and Cd muscle concentrations were ...significantly higher in the Indian-BET than in the Atlantic-BET, whereas the Indian-BET caught in the waters off South Africa revealed the highest As, Se, and Zn muscle concentrations. Accordingly, multidimensional scaling separated them into two oceanic groups. Positive linear relationships between muscle Cd concentration and fork length (FL) were established in both oceans. For the other elements, only muscle-Fe and FL relationship was found in the Atlantic-BET. 10.3% of BET > 145 cm FL from both oceans possessed muscle Cd concentrations exceeding the food safety limit (0.1 μg g−1 wet weight) set by the European Commission. Increased Cd, Cu and Zn pollution was found in the Atlantic Ocean compared with previous data, with higher levels found in the Indian Ocean.
Display omitted
•Bigeye tuna (BET) muscle metal levels reflect their geographical sampling sites.•Higher BET-As and -Cd muscle levels found in Indian Ocean than in Atlantic Ocean.•Positive relationships between muscle Cd levels and size revealed in the two Oceans.•10% of bigeye tuna > 145 cm had muscle Cd levels exceeding the food safety limit.•The muscle concentrations showed global oceanic metal pollution in recent 20 years.
Learning from a few examples (one/few-shot learning) on the fly is a key challenge for on-device machine intelligence. We present the first chip-level demonstration of one-shot learning with Stanford ...Associative memory for Programmable, Integrated Edge iNtelligence via life-long learning and Search (SAPIENS), a resistive random access memory (RRAM)-based non-volatile associative memory (AM) chip that serves as the backend for memory-augmented neural networks (MANNs). The 64-kb fully integrated RRAM-CMOS AM chip performs long-term feature embedding and retrieval, demonstrated on a 32-way one-shot learning task on the Omniglot dataset. Using only one example per class for 32 unseen classes during on-chip learning, SAPIENS achieves 79% measured inference accuracy on Omniglot, comparable to edge software model accuracy using five-level quantization (82%). It achieves an energy efficiency of 118 GOPS/W at 200 MHz for in-memory L1 distance computation and prediction. Multi-bank measurements on the same chip show that increasing the capacity from three banks (24 kb) to eight banks (64 kb) improves the chip accuracy from 73.5% to 79%, while minimizing the accuracy excursion due to bank-to-bank variability.
Background The risk of hepatocellular carcinoma (HCC) increases with increasing level of hepatitis B virus (HBV) in serum (viral load). However, it is unclear whether genetic characteristics of HBV, ...including HBV genotype and specific genetic mutations, contribute to the risk of HCC. We examined the HCC risk associated with HBV genotypes and common variants in the precore and basal core promoter (BCP) regions. Methods From January 5, 1991, to December 21, 1992, baseline blood samples were collected from 2762 Taiwanese men and women who were seropositive for HBV surface antigen but had not been diagnosed with HCC; the samples were tested for HBV viral load by real-time polymerase chain reaction and genotyped by melting curve analysis. Participants who had a baseline serum HBV DNA level greater than 104 copies/mL (n = 1526) were tested for the precore G1896A and BCP A1762T/G1764A mutants by direct sequencing. Incident cases of HCC were ascertained through follow-up examinations and computerized linkage to the National Cancer Registry and death certification profiles. A Cox proportional hazards model was used to estimate the risk of HCC associated with HBV genotype and precore and BCP mutants after adjustment for other risk factors. All statistical tests were two-sided. Results A total of 153 HCC cases occurred during 33 847 person-years of follow-up. The HCC incidence rates per 100 000 person-years for participants infected with HBV genotype B or C were 305.6 (95% confidence interval CI = 236.9 to 388.1) and 785.8 (95% CI = 626.8 to 972.9), respectively. Among participants with a baseline HBV DNA level of at least 104 copies/mL, HCC incidence per 100 000 person-years was higher for those with the precore G1896 (wild-type) variant than for those with the G1896A variant (955.5 95% CI = 749.0 to 1201.4 vs 269.4 95% CI = 172.6 to 400.9) and for those with the BCP A1762T/G1764A double mutant than for those with BCP A1762/G1764 (wild-type) variant (1149.2 95% CI = 872.6 to 1485.6 vs 358.7 95% CI = 255.1 to 490.4). The multivariable-adjusted hazard ratio of developing HCC was 1.76 (95% CI = 1.19 to 2.61) for genotype C vs genotype B, 0.34 (95% CI = 0.21 to 0.57) for precore G1896A vs wild type, and 1.73 (95% CI = 1.13 to 2.67) for BCP A1762T/G1764A vs wild type. Risk was highest among participants infected with genotype C HBV and wild type for the precore 1896 variant and mutant for the BCP 1762/1764 variant (adjusted hazard ratio = 2.99, 95% CI = 1.57 to 5.70, P < .001). Conclusions HBV genotype C and specific alleles of BCP and precore were associated with risk of HCC. These associations were independent of serum HBV DNA level.
Norovirus (NoV) infection is common in pediatric patients with immunodeficiency and is more likely to cause severe disease. Objective Our study aims to figure out the clinical differences and ...distribution of intestinal microbiota in immunocompromised children with NoV gastroenteritis.
Pediatric patients admitted to Shang-Ho Hospital with diagnosis of acute gastroenteritis including different immune status were enrolled and their medical records were reviewed. NoV gastroenteritis was validated using RT-PCR molecular methods. Viral shedding period was determined by real-time RT-PCR assays. Intestinal microbiota enrichment analysis was carried out by next generation sequencing after fecal DNA extraction and subsequent Linear Discriminant Analysis (LDA) Effect Size (LEfSe) method.
Significantly higher frequency of diarrhea mean, (IQR), 3.8 (3-5) /day and longer viral shedding time mean, IQR, 8.5 (5-13) days was found in immunocompromised NoV infections than in immunocompetent patients without NoV infections (p = 0.013*) and immunocompetent patients with NoV infections (p = 0.030**). The fever prevalence was significantly lower in immunocompromised NoV infections than in different immune or infection status. Intestinal microbiota metagenomics analysis showed no significant community richness difference while the LEfSe analysis showed a significant difference in commensal richness at the phylum level, the family level, and the genus level in patients under different immune status.
We evaluated the clinical significances and microbiota composition in immunocompromised children with norovirus gastroenteritis. This will further facilitate studies of the interaction between the intestinal microbiota in such patients with precise determination of their bacterial infection control and probiotic supplements strategy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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