All-Electrical Skyrmionic Bits in a Chiral Magnetic Tunnel Junction

Topological spin textures such as magnetic skyrmions hold considerable promise as robust, nanometre-scale, mobile bits for sustainable computing. A longstanding roadblock to unleashing their potential is the absence of a device enabling deterministic electrical readout of individual spin textures. Here we present the wafer-scale realization of a nanoscale chiral magnetic tunnel junction (MTJ) hosting a single, ambient skyrmion. Using a suite of electrical and multi-modal imaging techniques, we show that the MTJ nucleates skyrmions of fixed polarity, whose large readout signal - 20-70% relative to uniform states - corresponds directly to skyrmion size. Further, the MTJ exploits complementary mechanisms to stabilize distinctly sized skyrmions at zero field, thereby realizing three nonvolatile electrical states. Crucially, it can write and delete skyrmions using current densities 1,000 times lower than state-of-the-art. These results provide a platform to incorporate readout and manipulation of skyrmionic bits across myriad device architectures, and a springboard to harness chiral spin textures for multi-bit memory and unconventional computing.Comment: 8 pages, 5 figure

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

DNA metabarcoding unravels unknown diversity and distribution patterns of tropical freshwater invertebrates

Tropical freshwater invertebrate species are becoming extinct without being described, and effective conservation is hampered by a lack of taxonomic and distribution data. DNA metabarcoding is a promising tool for rapid biodiversity assessments that has never been applied to tropical freshwater invertebrates across large spatial and taxonomic scales. Here we use DNA metabarcoding to comprehensively assess the benthic freshwater invertebrate fauna of the Perak River basin, Malaysia. Specific objectives were to: (1) assess performance of two DNA metabarcoding protocols; (2) identify gaps in reference databases; (3) generate new data on species diversity and distribution; and (4) draw conclusions regarding the potential value of DNA metabarcoding in tropical freshwater conservation. Organisms were collected by hand and net at 34 sites and divided into small (retained in 0.5-mm but passing through 1-mm mesh) and large (retained in 1-mm mesh) fractions, and a 313-bp cytochrome c oxidase subunit I fragment amplified and sequenced using general Metazoa primers. Bioinformatic analysis resulted in 468 operational taxonomic units (~species) from 12 phyla. Only 29% of species could be assigned binominal names through matches to public sequence libraries, indicating varying levels of library completeness across Orders. Extraction of small-fraction DNA with a soil kit resulted in a significantly higher species count than with a general kit, but this was not even across taxa. Metabarcoding (amplification) success rate, estimated via comparison to morphological identifications of the large-fraction specimens, was high in most taxa analysed but low, for example, in ampullariid and viviparid gastropods. Conversely, a large proportion of species-site records for Decapoda and Bivalvia came from metabarcoding only. Species richness averaged 29 ± 16 species per site, dominated by Diptera, Annelida, and Odonata, and was particularly high in tributaries of the mountainous Titiwangsa Range. At least eight species are new records for Malaysia, including the non-natives Ferrissia fragilis (Gastropoda) and Dugesia notogaea (Platyhelminthes). Our study showed that DNA metabarcoding is generally more effective in detecting tropical freshwater invertebrate species than traditional morphological approaches, and can efficiently improve knowledge of distribution patterns and ranges of native and non-native species. However, current gaps in reference databases, particularly for bioindicator taxa, such as the Plecoptera, Ephemeroptera, and Coleoptera, need to be addressed urgently

Life Cycle-Dependent Cytoskeletal Modifications in Plasmodium falciparum Infected Erythrocytes

10.1371/journal.pone.0061170PLoS ONE84

Acid Solution Is a Suitable Medium for Introducing QX-314 into Nociceptors through TRPV1 Channels to Produce Sensory-Specific Analgesic Effects

BACKGROUND: Previous studies have demonstrated that QX-314, an intracellular sodium channel blocker, can enter into nociceptors through capsaicin-activated TRPV1 or permeation of the membrane by chemical enhancers to produce a sensory-selective blockade. However, the obvious side effects of these combinations limit the application of QX-314. A new strategy for targeting delivery of QX-314 into nociceptors needs further investigation. The aim of this study is to test whether acidic QX-314, when dissolves in acidic solution directly, can enter into nociceptors through acid-activated TRPV1 and block sodium channels from the intracellular side to produce a sensory-specific analgesic effect. METHODOLOGY/PRINCIPAL FINDINGS: Acidic solution or noradrenaline was injected intraplantarly to induce acute pain behavior in mice. A chronic constrictive injury model was performed to induce chronic neuropathic pain. A sciatic nerve blockade model was used to evaluate the sensory-specific analgesic effects of acidic QX-314. Thermal and mechanical hyperalgesia were measured by using radiant heat and electronic von Frey filaments test. Spinal Fos protein expression was determined by immunohistochemistry. The expression of p-ERK was detected by western blot assay. Whole cell clamp recording was performed to measure action potentials and total sodium current in rats DRG neurons. We found that pH 5.0 PBS solution induced behavioral hyperalgesia accompanied with the increased expression of spinal Fos protein and p-ERK. Pretreatment with pH 5.0 QX-314, and not pH 7.4 QX-314, alleviated pain behavior, inhibited the increased spinal Fos protein and p-ERK expression induced by pH 5.0 PBS or norepinephrine, blocked sodium currents and abolished the production of action potentials evoked by current injection. The above effects were prevented by TRPV1 channel inhibitor SB366791, but not by ASIC channel inhibitor amiloride. Furthermore, acidic QX-314 employed adjacent to the sciatic nerve selectively blocked the sensory but not the motor functions in naïve and CCI mice. CONCLUSIONS/SIGNIFICANCE: Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce a sensory-specific analgesic effect

DNA metabarcoding unravels unknown diversity and distribution patterns of tropical freshwater invertebrates

Tropical freshwater invertebrate species are becoming extinct without being described, and effective conservation is hampered by a lack of taxonomic and distribution data. DNA metabarcoding is a promising tool for rapid biodiversity assessments that has never been applied to tropical freshwater invertebrates across large spatial and taxonomic scales. Here we use DNA metabarcoding to comprehensively assess the benthic freshwater invertebrate fauna of the Perak River basin, Malaysia. Specific objectives were to: (1) assess performance of two DNA metabarcoding protocols; (2) identify gaps in reference databases; (3) generate new data on species diversity and distribution; and (4) draw conclusions regarding the potential value of DNA metabarcoding in tropical freshwater conservation. Organisms were collected by hand and net at 34 sites and divided into small (retained in 0.5-mm but passing through 1-mm mesh) and large (retained in 1-mm mesh) fractions, and a 313-bp cytochrome c oxidase subunit I fragment amplified and sequenced using general Metazoa primers. Bioinformatic analysis resulted in 468 operational taxonomic units (~species) from 12 phyla. Only 29% of species could be assigned binominal names through matches to public sequence libraries, indicating varying levels of library completeness across Orders. Extraction of small-fraction DNA with a soil kit resulted in a significantly higher species count than with a general kit, but this was not even across taxa. Metabarcoding (amplification) success rate, estimated via comparison to morphological identifications of the large-fraction specimens, was high in most taxa analysed but low, for example, in ampullariid and viviparid gastropods. Conversely, a large proportion of species-site records for Decapoda and Bivalvia came from metabarcoding only. Species richness averaged 29 ± 16 species per site, dominated by Diptera, Annelida, and Odonata, and was particularly high in tributaries of the mountainous Titiwangsa Range. At least eight species are new records for Malaysia, including the non-natives Ferrissia fragilis (Gastropoda) and Dugesia notogaea (Platyhelminthes). Our study showed that DNA metabarcoding is generally more effective in detecting tropical freshwater invertebrate species than traditional morphological approaches, and can efficiently improve knowledge of distribution patterns and ranges of native and non-native species. However, current gaps in reference databases, particularly for bioindicator taxa, such as the Plecoptera, Ephemeroptera, and Coleoptera, need to be addressed urgently

Distributed evolutionary algorithms and their models: A survey of the state-of-the-art

The increasing complexity of real-world optimization problems raises new challenges to evolutionary computation. Responding to these challenges, distributed evolutionary computation has received considerable attention over the past decade. This article provides a comprehensive survey of the state-of-the-art distributed evolutionary algorithms and models, which have been classified into two groups according to their task division mechanism. Population-distributed models are presented with master-slave, island, cellular, hierarchical, and pool architectures, which parallelize an evolution task at population, individual, or operation levels. Dimension-distributed models include coevolution and multi-agent models, which focus on dimension reduction. Insights into the models, such as synchronization, homogeneity, communication, topology, speedup, advantages and disadvantages are also presented and discussed. The study of these models helps guide future development of different and/or improved algorithms. Also highlighted are recent hotspots in this area, including the cloud and MapReduce-based implementations, GPU and CUDA-based implementations, distributed evolutionary multiobjective optimization, and real-world applications. Further, a number of future research directions have been discussed, with a conclusion that the development of distributed evolutionary computation will continue to flourish

Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86

The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses

A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

<p>Abstract</p> <p>Background</p> <p>According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer.</p> <p>Methods</p> <p>This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study.</p> <p>Results</p> <p>Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)).</p> <p>Conclusions</p> <p>The younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.</p