End-to-End Deep Transfer Learning for Calibration-free Motor Imagery Brain Computer Interfaces

A major issue in Motor Imagery Brain-Computer Interfaces (MI-BCIs) is their poor classification accuracy and the large amount of data that is required for subject-specific calibration. This makes BCIs less accessible to general users in out-of-the-lab applications. This study employed deep transfer learning for development of calibration-free subject-independent MI-BCI classifiers. Unlike earlier works that applied signal preprocessing and feature engineering steps in transfer learning, this study adopted an end-to-end deep learning approach on raw EEG signals. Three deep learning models (MIN2Net, EEGNet and DeepConvNet) were trained and compared using an openly available dataset. The dataset contained EEG signals from 55 subjects who conducted a left- vs. right-hand motor imagery task. To evaluate the performance of each model, a leave-one-subject-out cross validation was used. The results of the models differed significantly. MIN2Net was not able to differentiate right- vs. left-hand motor imagery of new users, with a median accuracy of 51.7%. The other two models performed better, with median accuracies of 62.5% for EEGNet and 59.2% for DeepConvNet. These accuracies do not reach the required threshold of 70% needed for significant control, however, they are similar to the accuracies of these models when tested on other datasets without transfer learning

North Atlantic surface ocean warming and salinization in response to middle Eocene greenhouse warming

Quantitative reconstructions of hydrological change during ancient greenhouse warming events provide valuable insight into warmer-than-modern hydrological cycles but are limited by paleoclimate proxy uncertainties. We present sea surface temperature (SST) records and seawater oxygen isotope (δ18Osw) estimates for the Middle Eocene Climatic Optimum (MECO), using coupled carbonate clumped isotope (Δ47) and oxygen isotope (δ18Oc) data of well-preserved planktonic foraminifera from the North Atlantic Newfoundland Drifts. These indicate a transient ~3°C warming across the MECO, with absolute temperatures generally in accordance with trace element (Mg/Ca)–based SSTs but lower than biomarker-based SSTs for the same interval. We find a transient ~0.5‰ shift toward higher (δ18Osw), which implies increased salinity in the North Atlantic subtropical gyre and potentially a poleward expansion of its northern boundary in response to greenhouse warming. These observations provide constraints on dynamic ocean response to warming events, which are consistent with theory and model simulations predicting an enhanced hydrological cycle under global warming

Assembly and expression of a synthetic gene encoding the antigen Pfs48/45 of the human malaria parasite Plasmodium falciparum in yeast.

Contains fulltext : 112872.pdf (publisher's version ) (Closed access)Pfs48/45 is an important transmission-blocking vaccine candidate antigen of the human malaria parasite Plasmodium falciparum. This study was aimed at synthesis of recombinant Pfs48/45 containing conformation-constrained epitopes of the native antigen in yeast. Since in the yeast Saccharomyces cerevisiae induction of gene-expression led to prematurely terminated transcripts, an entirely synthetic gene of higher GC content was assembled. Replacement of the AT rich natural gene by the synthetic gene relieved the observed premature transcription termination. Nevertheless, recombinant protein expression could not be detected. In contrast, in the yeast Pichia pastoris low levels of recombinant Pfs48/45 were produced upon induction of synthetic gene expression. The recombinant protein was shown to be disulphide-bridge constrained, but was not recognised by transmission-blocking antibodies and did not induce transmission-blocking sera in mice

Mass Spectrometric Identification of Cardiac Troponin T in Urine of Patients Suffering from Acute Myocardial Infarction

Background: Because of its high cardiospecificity, cardiac troponin T (cTnT) is one of the first-choice biomarkers to diagnose acute myocardial infarction(AMI). cTnT is extensively fragmented in serum of patients suffering from AMI. However,it is currently unknown whether all cTnT is completely degraded in the body or whether some cTnT fragments can leave the body via urine.The aim of the present study is to develop a method for the detection of cTnT in urine and to examine whether cTnTis detectable in patient urine. Methods: Proteins in urine samples of 20 patients were precipitated using a cTnT-specific immunoprecipitation technique and a nonspecific acetonitrile protein precipitation. After in-solution digestion of the precipitated proteins, the resulting peptides were separated and analyzed using HPLC and mass spectrometry with a targeted selected ion monitoring assay with data-dependent tandem mass spectrometry(t-SIM/dd-MS2). Results: Thet-SIM/dd-MS2 assay was validated using a synthetic peptide standard containing 10 specific cTnTpeptides of interest and with purified human intact cTnT spiked in urine from healthy individuals. Using this assay, 6 different cTnT-specific peptides were identified inurine samples from 3 different patients,all suffering from AMI. Conclusions: We show here for the first time that cTnT can be present in the urine of AMI patients using a targeted LC-MS/MSassay.Whether the presence of cTnT inurine reflects a physiological or pathophysiological process still needs to be elucidated

Proteolytic processing and primary structure of Plasmodium falciparum apical membrane antigen-1.

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a malaria merozoite integral membrane protein that plays an essential but poorly understood role in invasion of host erythrocytes. The PfAMA-1 ectodomain comprises three disulfide-constrained domains, the first of which (domain I) is preceded by an N-terminal prosequence. PfAMA-1 is initially routed to secretory organelles at the apical end of the merozoite, where the 83-kDa precursor (PfAMA-1(83)) is converted to a 66-kDa form (PfAMA-1(66)). At about the time of erythrocyte invasion, PfAMA-1(66) selectively translocates onto the merozoite surface. Here we use direct microsequencing and mass spectrometric peptide mass fingerprinting to characterize in detail the primary structure and proteolytic processing of PfAMA-1. We have determined the site at which processing takes place to convert PfAMA-1(83) to PfAMA-1(66) and have shown that both species possess a completely intact and unmodified transmembrane and cytoplasmic domain. Following relocation to the merozoite surface, PfAMA-1(66) is further proteolytically cleaved at one of two alternative sites, either between domains II and III, or at a membrane-proximal site following domain III. As a result, the bulk of the ectodomain is shed from the parasite surface in the form of two soluble fragments of 44 and 48 kDa. PfAMA-1 is not detectably modified by the addition of N-linked oligosaccharides

A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage.

Erythrocyte invasion by the malaria merozoite is accompanied by the regulated discharge of apically located secretory organelles called micronemes. Plasmodium falciparum apical membrane antigen-1 (PfAMA-1), which plays an indispensable role in invasion, translocates from micronemes onto the parasite surface and is proteolytically shed in a soluble form during invasion. We have previously proposed, on the basis of incomplete mass spectrometric mapping data, that PfAMA-1 shedding results from cleavage at two alternative positions. We now show conclusively that the PfAMA-1 ectodomain is shed from the merozoite solely as a result of cleavage at a single site, just 29 residues away from the predicted transmembrane-spanning sequence. Remarkably, this cleavage is mediated by the same membrane-bound parasite serine protease as that responsible for shedding of the merozoite surface protein-1 (MSP-1) complex, an abundant, glycosylphosphatidylinositol-anchored multiprotein complex. Processing of MSP-1 is essential for invasion. Our results indicate the presence on the merozoite surface of a multifunctional serine sheddase with a broad substrate specificity. We further demonstrate that translocation and shedding of PfAMA-1 is an actin-independent process

Synchronous tropical and polar temperature evolution in the Eocene

Palaeoclimate reconstructions of periods with warm climates and high atmospheric CO2 concentrations are crucial for developing better projections of future climate change. Deep-ocean1,2 and high-latitude3 palaeotemperature proxies demonstrate that the Eocene epoch (56 to 34 million years ago) encompasses the warmest interval of the past 66 million years, followed by cooling towards the eventual establishment of ice caps on Antarctica. Eocene polar warmth is well established, so the main obstacle in quantifying the evolution of key climate parameters, such as global average temperature change and its polar amplification, is the lack of continuous high-quality tropical temperature reconstructions. Here we present a continuous Eocene equatorial sea surface temperature record, based on biomarker palaeothermometry applied on Atlantic Ocean sediments. We combine this record with the sparse existing data4-6 to construct a 26-million-year multi-proxy, multi-site stack of Eocene tropical climate evolution. We find that tropical and deep-ocean temperatures changed in parallel, under the influence of both long-term climate trends and short-lived events. This is consistent with the hypothesis that greenhouse gas forcing7,8, rather than changes in ocean circulation9,10, was the main driver of Eocene climate. Moreover, we observe a strong linear relationship between tropical and deep-ocean temperatures, which implies a constant polar amplification factor throughout the generally ice-free Eocene. Quantitative comparison with fully coupled climate model simulations indicates that global average temperatures were about 29, 26, 23 and 19 degrees Celsius in the early, early middle, late middle and late Eocene, respectively, compared to the preindustrial temperature of 14.4 degrees Celsius. Finally, combining proxy- and model-based temperature estimates with available CO2 reconstructions8 yields estimates of an Eocene Earth system sensitivity of 0.9 to 2.3 kelvin per watt per square metre at 68 per cent probability, consistent with the high end of previous estimates11

A conserved subtilisin-like protein TgSUB1 in microneme organelles of Toxoplasma gondii.

Proteolytic processing plays a significant role in the process of invasion by the obligate intracellular parasite Toxoplasma gondii. We have cloned a gene, TgSUB1, encoding for a subtilisin-type serine protease found in T. gondii tachyzoites. TgSUB1 protein is homologous to other Apicomplexan and bacterial subtilisins and is processed within the secretory pathway of the parasite. Initial cleavage occurs in the endoplasmic reticulum, after which the protein is transported to micronemes, vesicles that secrete early during host cell invasion. Upon stimulation of microneme secretion, TgSUB1 is cleaved into smaller products that are secreted from the parasite. This secondary processing is inhibited by brefeldin A and serine protease inhibitors. TgSUB1 is a candidate processing enzyme for several microneme proteins cleaved within the secretory pathway or during invasion

North Atlantic surface ocean warming and salinization in response to middle Eocene greenhouse warming

Quantitative reconstructions of hydrological change during ancient greenhouse warming events provide valuable insight into warmer-than-modern hydrological cycles but are limited by paleoclimate proxy uncertainties. We present sea surface temperature (SST) records and seawater oxygen isotope (δ18Osw) estimates for the Middle Eocene Climatic Optimum (MECO), using coupled carbonate clumped isotope (Δ47) and oxygen isotope (δ18Oc) data of well-preserved planktonic foraminifera from the North Atlantic Newfoundland Drifts. These indicate a transient ~3°C warming across the MECO, with absolute temperatures generally in accordance with trace element (Mg/Ca)–based SSTs but lower than biomarker-based SSTs for the same interval. We find a transient ~0.5‰ shift toward higher δ18Osw, which implies increased salinity in the North Atlantic subtropical gyre and potentially a poleward expansion of its northern boundary in response to greenhouse warming. These observations provide constraints on dynamic ocean response to warming events, which are consistent with theory and model simulations predicting an enhanced hydrological cycle under global warming

North Atlantic surface ocean warming and salinization in response to middle Eocene greenhouse warming

Quantitative reconstructions of hydrological change during ancient greenhouse warming events provide valuable insight into warmer-than-modern hydrological cycles but are limited by paleoclimate proxy uncertainties. We present sea surface temperature (SST) records and seawater oxygen isotope (δ18Osw) estimates for the Middle Eocene Climatic Optimum (MECO), using coupled carbonate clumped isotope (Δ47) and oxygen isotope (δ18Oc) data of well-preserved planktonic foraminifera from the North Atlantic Newfoundland Drifts. These indicate a transient ~3°C warming across the MECO, with absolute temperatures generally in accordance with trace element (Mg/Ca)–based SSTs but lower than biomarker-based SSTs for the same interval. We find a transient ~0.5 ‰ shift toward higher δ18Osw, which implies increased salinity in the North Atlantic subtropical gyre and potentially a poleward expansion of its northern boundary in response to greenhouse warming. These observations provide constraints on dynamic ocean response to warming events, which are consistent with theory and model simulations predicting an enhanced hydrological cycle under global warming