Miracle-dz/UniFAR-FTUs huggingface dataset:
A Statistical Model of Protein Sequence Similarity and Function Similarity Reveals Overly-Specific Function Predictions

Background Predicting protein function from primary sequence is an important open problem in modern biology. Not only are there many thousands of proteins of unknown function, current approaches for predicting function must be improved upon. One problem in particular is overly-specific function predictions which we address here with a new statistical model of the relationship between protein sequence similarity and protein function similarity. Methodology Our statistical model is based on sets of proteins with experimentally validated functions and numeric measures of function specificity and function similarity derived from the Gene Ontology. The model predicts the similarity of function between two proteins given their amino acid sequence similarity measured by statistics from the BLAST sequence alignment algorithm. A novel aspect of our model is that it predicts the degree of function similarity shared between two proteins over a continuous range of sequence similarity, facilitating prediction of function with an appropriate level of specificity. Significance Our model shows nearly exact function similarity for proteins with high sequence similarity (bit score >244.7, e-value >1e−62, non-redundant NCBI protein database (NRDB)) and only small likelihood of specific function match for proteins with low sequence similarity (bit score <54.6, e-value <1e−05, NRDB). For sequence similarity ranges in between our annotation model shows an increasing relationship between function similarity and sequence similarity, but with considerable variability. We applied the model to a large set of proteins of unknown function, and predicted functions for thousands of these proteins ranging from general to very specific. We also applied the model to a data set of proteins with previously assigned, specific functions that were electronically based. We show that, on average, these prior function predictions are more specific (quite possibly overly-specific) compared to predictions from our model that is based on proteins with experimentally determined function.
Risk of hair loss with different antidepressants: a comparative retrospective cohort study

The aim of this study was to quantify the risk of hair loss with different antidepressants. A retrospective cohort study design using a large health claims database in the USA from 2006 to 2014 was utilized. A cohort of new user and mutually exclusive users of fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion were followed to the first diagnosis of alopecia. The cohort was comprised of 1 025 140 new users of fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion, with sertraline the most commonly prescribed (N=190 227) and fluvoxamine (N=3010) the least prescribed. Compared with bupropion, all other antidepressants had a lower risk of hair loss, with fluoxetine and paroxetine having the lowest risk [hazard ratio (HR)=0.68, 95% confidence interval (CI): 0.63–0.74, HR=0.68, 95% CI: 0.62–0.74, respectively] and fluvoxamine having the highest risk (HR=0.93, 95% CI: 0.64–1.37). Compared with fluoxetine, bupropion had the highest risk of hair loss (HR=1.46, 95% CI: 1.35–1.58, number needed to harm=242 for 2 years) and paroxetine had the lowest risk (HR=0.99, 95% CI: 0.90–1.09). The results of this large population-based cohort study suggest an increase in the risk of hair loss with bupropion compared with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, whereas paroxetine had the lowest risk.
Targeted proteomic dissection of Toxoplasma cytoskeleton sub‐compartments using MORN1

The basal complex in Toxoplasma functions as the contractile ring in the cell division process. Basal complex contraction tapers the daughter cytoskeleton toward the basal end and is required for daughter segregation. We have previously shown that the protein MORN1 is essential for basal complex assembly and likely acts as a scaffolding protein. To further our understanding of the basal complex, we combined subcellular fractionation with an affinity purification of the MORN1 complex and identified its protein composition. We identified two new components of the basal complex, one of which uniquely associated with the basal complex in mature parasites, the first of its kind. In addition, we identified several other novel cytoskeleton proteins with different spatiotemporal dynamics throughout cell division. Since many of these proteins are unique to Apicomplexa this study significantly contributes to the annotation of their unique cytoskeleton. Furthermore, we show that G‐actin binding protein TgCAP is localized at the apical cap region in intracellular parasites, but quickly redistributes to a cytoplasmic localization pattern upon egress. © 2012 Wiley Periodicals, Inc.
IATAC: a smart predictor to turn-off L2 cache lines

As technology evolves, power dissipation increases and cooling systems become more complex and expensive. There are two main sources of power dissipation in a processor: dynamic power and leakage. Dynamic power has been the most significant factor, but leakage will become increasingly significant in future. It is predicted that leakage will shortly be the most significant cost as it grows at about a 5× rate per generation. Thus, reducing leakage is essential for future processor design. Since large caches occupy most of the area, they are one of the leakiest structures in the chip and hence, a main source of energy consumption for future processors.This paper introduces IATAC (inter-access time per access count), a new hardware technique to reduce cache leakage for L2 caches. IATAC dynamically adapts the cache size to the program requirements turning off cache lines whose content is not likely to be reused. Our evaluation shows that this approach outperforms all previous state-of-the-art techniques. IATAC turns off 65% of the cache lines across different L2 cache configurations with a very small performance degradation of around 2%.
Online anomal movement detection based on unsupervised incremental learning

We propose an online anomal movement detection method using incremental unsupervised learning. As the feature for discrimination, we extract the principal component of the spatio-temporal feature by incremental PCA. We then detect anomal movements by an incremental 1-class SVM. In order to use principal component as the feature for discrimination while supporting incrementation of the subspace, we modify the SVM kernel function to take account of the difference in distance scale between the principal component feature vectors and that of the feature vectors after the subspace is incremented. This allows us to efficiently conduct the relearning process even though the dimension of the original input spatio-temporal feature is high. Experiments show that anomal scenes can be detected without the cost of preparing a lot of labeled data for preliminary learning.
Eikenella corrodens Phase Variation Involves a Posttranslational Event in Pilus Formation

ABSTRACT The human pathogen Eikenella corrodens synthesizes type IV pili and exhibits a phase variation involving the irreversible transition from piliated to nonpiliated variants. On solid medium, piliated variants form small (S-phase), corroding colonies whereas nonpiliated variants form large (L-phase), noncorroding colonies. We are studying the molecular basis of this phase variation in the clinical isolate E. corrodens VA1. A genomic fragment encoding the major type IV pilin was cloned from the S-phase variant of strain VA1. Sequence analysis of the fragment revealed four tandemly arranged potential open reading frames (ORFs), designatedpilA1, pilA2, pilB, andhagA. Both pilA1 and pilA2 predict a type IV pilin. The protein predicted by pilB shares sequence identity with the Dichelobacter nodosus FimB fimbrial assembly protein. The protein predicted by hagAresembles a hemagglutinin. The region containing these four ORFs was designated the pilA locus. DNA hybridization and sequence analysis showed that the pilA locus of an L-phase variant of strain VA1 was identical to that of the S-phase variant. An abundantpilA1 transcript initiating upstream of pilA1and terminating at a predicted hairpin structure betweenpilA1 and pilA2 was detected by several assays, as was a less abundant read-through transcript encompassingpilA1, pilA2, and pilB. Transcription from the pilA locus was nearly indistinguishable between S- and L-phase variants. Electron microscopy and immunochemical analysis showed that S-phase variants synthesize, export, and assemble pilin into pili. In contrast, L-phase variants synthesize pilin but do not export and assemble it into pili. These data suggest that a posttranslational event, possibly involving an alteration in pilin export and assembly, is responsible for phase variation in E. corrodens.
Long term outcome of patients with neurotic illness in general practice

Abstract Objective: To determine the 11 year outcome of neurotic disorder in general practice. Design: Cohort study over 11 years. Setting: Two general practices in Warwickshire England. Subjects: 100 patients selected to be representative of those identified nationally by general practitioners as having neurotic disorders. Main outcome measures: Mortality, morbidity, and use of health services. Results: At 11 years 87 subjects were traced. The 11 year standardised mortality ratio was 173 (95% confidence interval 164 to 200). 47 were cases on the general health questionnaire, 32 had a relapsing or chronic psychiatric course, and 49 a relapsing or chronic physical course. Treatment for psychiatric illness was mainly drugs. The mean number of consultations per year was 10.8 (median 8.7). A persistent psychiatric diagnosis at one year follow up was associated with high attendance (>12 visits a year for 11 years) at follow up after age, sex, and physical illness were adjusted for. Severity of psychiatric illness (general health questionnaire score) at outset predicted general health questionnaire score at 11 year follow up, course of psychiatric illness, and high consultation rate. Conclusion: These data support the view that a neurotic illness can become chronic and is associated with raised mortality from all causes and high use of services. Such patients need effective intervention, particularly those with a more severe illness who do not recover within one year. Key messages In this study almost half had a chronic course over 11 years Chronic neurotic disorder is associated with high consultation regardless of physical illness Initial severity at diagnosis is the best predictor of long term outcome and consultation rate Practices need to develop systems to identify and manage effectively people with these common mental disorders
Precise determination of the heat delivery during in vivo magnetic nanoparticle hyperthermia with infrared thermography

Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal’s surface. The results indicate that temperature errors as large as 7 ∘C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.
Adaptive Parameter Estimation, Modeling and Patient-Specific Classification of Electrocardiogram Signals

Adaptive processing and classification of electrocardiogram (ECG) signals are important in eliminating the strenuous process of manually annotating ECG recordings for clinical use. Such algorithms require robust models whose parameters can adequately describe the ECG signals. Although different dynamic statistical models describing ECG signals currently exist, they depend considerably on a priori information and user-specified model parameters. Also, ECG beat morphologies, which vary greatly across patients and disease states, cannot be uniquely characterized by a single model. In this work, sequential Bayesian based methods are used to appropriately model and adaptively select the corresponding model parameters of ECG signals. An adaptive framework based on a sequential Bayesian tracking method is proposed to adaptively select the cardiac parameters that minimize the estimation error, thus precluding the need for pre-processing. Simulations using real ECG data from the online Physionet database demonstrate the improvement in performance of the proposed algorithm in accurately estimating critical heart disease parameters. In addition, two new approaches to ECG modeling are presented using the interacting multiple model and the sequential Markov chain Monte Carlo technique with adaptive model selection. Both these methods can adaptively choose between different models for various ECG beat morphologies without requiring prior ECG information, as demonstrated by using real ECG signals. A supervised Bayesian maximum-likelihood (ML) based classifier uses the estimated model parameters to classify different types of cardiac arrhythmias. However, the non-availability of sufficient amounts of representative training data and the large inter-patient variability pose a challenge to the existing supervised learning algorithms, resulting in a poor classification performance. In addition,
Calculation of Bit Error Rates in Optical Systems With Silicon Photonic Wires

A theoretical approach to calculate the bit error rate (BER) in optical systems containing silicon photonic wires (Si-PhWs) is presented. Specifically, the optical link consists of a single-mode silicon-on-insulator strip waveguide followed by a direct-detection optical receiver containing an optical filter, an ideal square-law photodetector, and an electrical filter. We assume that the optical input consists of a superposition of a nonreturn-to-zero ON-OFF keying modulated optical signal and an additive white Gaussian noise, the BER of the transmitted optical signal being calculated using the time domain Karhunen-Loève expansion method. The propagation of the optical signal in the Si-PhW is described by employing both a rigorous theoretical model that incorporates all relevant linear and nonlinear optical effects and the mutual interaction between the free carriers and the optical field, as well as a linearized model valid in the low-noise power regime. These analytical and computational tools are then used to comprehensively investigate the influence of the parameters characterizing the waveguide and optical signal on the transmission BER.
Re‐constructing the relationship between drama and English: Student‐teachers’ perspectives at the end of an initial teacher education year

Abstract My research draws on data from focus group interviews with student‐teachers1 which took place near the end of a one‐year initial teacher education course. One group was studying to become teachers of secondary English, and the other secondary drama teachers. Both took part in a ‘diamond twelve’ activity highlighting different perspectives on the content and purpose of drama in the English curriculum. The article explores how the participants construct the relationship between their two subjects, and raises questions about the nature and relevance of the continuing association between drama and English that is enshrined in the National Curriculum for England and Wales.
Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.
Translational Research Insights From Completed HIV Vaccine Efficacy Trials

Abstract:The development of a safe and effective HIV vaccine remains a challenge. The modest efficacy seen in the RV144 vaccine trial represented an important milestone for the field. Results from all efficacy studies done to date have generated new information, which has advanced the HIV vaccine field in important ways. In this article, we review the translational research insights from the vaccine efficacy trials completed and fully analyzed to date. We also describe the recent advances in the search for broadly neutralizing antibodies and discuss potential approaches to circumvent the challenge posed by the enormous diversity of HIV-1. The experience from the past 5 years highlights the importance of conducting efficacy studies that continue to move us closer toward the goal of a safe, effective, durable, and universal HIV preventive vaccine.
The yeast Mcm1 protein is regulated posttranscriptionally by the flux of glycolysis

Mcm1 is a multifunctional protein which plays a role both in the initiation of DNA replication and in the transcriptional regulation of diverse genes in Saccharomyces cerevisiae. The mcm1-1 mutation results in instability of minichromosomes and alpha-specific sterility. Second-site suppressors that restore minichromosome stability but not fertility to the mcm1-1 mutant were isolated. Two of the suppressors, pgm1-1 and pgm1-2, are mutant alleles of PGM1 which encodes a glycolytic enzyme, phosphoglycerate mutase. We show that the pgm1-1 mutation suppresses the minichromosome maintenance (Mcm) defect by increasing the protein activity or level of Mcm1-1 posttranscriptionally. This increase in the intracellular Mcm1-1 activity is sufficient to suppress the Mcm defect but only minimally suppresses the mating defect. Mutations in genes encoding other glycolytic enzymes, such as eno2::URA3, can also suppress the Mcm phenotype of mcm1-1. Suppression by these glycolytic enzyme mutations correlates with a reduced rate of glycolysis rather than a reduced rate of cell growth. This study suggests that in response to changes in their nutritional states yeast cells may attain homeostasis by modulating the activity of global regulators like Mcm1, which plays a central role in the regulation of energy-expensive anabolic processes.
Visible Light Imaging of Small Animals

A visible light imaging system constructed from commercially available products is described. The utility of this detector system in the context of Bioluminescent and Fluorescent imaging is assessed through studies of the effects of temperature on CCD performance, expression of green fluorescent protein in Xenapous frog embryos, attenuation of light by biological tissue, and the overall performance of this imaging system.
mlRho – a program for estimating the population mutation and recombination rates from shotgun‐sequenced diploid genomes

Improvements in sequencing technology over the past 5 years are leading to routine application of shotgun sequencing in the fields of ecology and evolution. However, the theory to estimate evolutionary parameters from these data is still being worked out. Here we present an extension and implementation of part of this theory, mlRho. This program can efficiently compute the following three maximum likelihood estimators based on shotgun sequence data obtained from single diploid individuals: the population mutation rate (4Neμ), the sequencing error rate, and the population recombination rate (4Nec). We demonstrate the accuracy of mlRho by applying it to simulated data sets. In addition, we analyse the genomes of the sea squirt Ciona intestinalis and the water flea Daphnia pulex. Ciona intestinalis is an obligate outcrosser, while D. pulex is a cyclic parthenogen, and we discuss how these contrasting life histories are reflected in our parameter estimates. The program mlRho is freely available from http://guanine.evolbio. mpg.de/mlRho.
Research on water quality predictive model based on robust splines partial least squares

Considering the correlation, nonlinearity and outliers of water quality data, a Robust Splines Partial Least Squares (RSPLS) algorithm is proposed and applied to study the predictive model of water quality. The nonlinear relationship of the measured data was transformed into quasi-linear by splines. Then robust method, which distributed different weights to the measured data, was implemented into the iterative operation of the transformed data to establish a robust nonlinear data predictive model of water quality. The method can overcome the multi-collinear of the variables and the outliers. The simulation of the algorithm shows that the water quality predictive model can predict the water quality accurately.