Miracle-dz/UniFAR-FTUs huggingface dataset:
Statistical Methods for Identifying Sequence Motifs Affecting Point Mutations

Mutation processes differ between types of point mutation, genomic locations, cells, and biological species. For some point mutations, specific neighboring bases are known to be mechanistically influential. Beyond these cases, numerous questions remain unresolved, including: what are the sequence motifs that affect point mutations? How large are the motifs? Are they strand symmetric? And, do they vary between samples? We present new log-linear models that allow explicit examination of these questions, along with sequence logo style visualization to enable identifying specific motifs. We demonstrate the performance of these methods by analyzing mutation processes in human germline and malignant melanoma. We recapitulate the known CpG effect, and identify novel motifs, including a highly significant motif associated with A→G mutations. We show that major effects of neighbors on germline mutation lie within ±2 of the mutating base. Models are also presented for contrasting the entire mutation spectra (the distribution of the different point mutations). We show the spectra vary significantly between autosomes and X-chromosome, with a difference in T→C transition dominating. Analyses of malignant melanoma confirmed reported characteristic features of this cancer, including statistically significant strand asymmetry, and markedly different neighboring influences. The methods we present are made freely available as a Python library https://bitbucket.org/pycogent3/mutationmotif.
Distinct Signaling Events Downstream of mTOR Cooperate To Mediate the Effects of Amino Acids and Insulin on Initiation Factor 4E-Binding Proteins

ABSTRACT Signaling through the mammalian target of rapamycin (mTOR) controls cell size and growth as well as other functions, and it is a potential therapeutic target for graft rejection, certain cancers, and disorders characterized by inappropriate cell or tissue growth. mTOR signaling is positively regulated by hormones or growth factors and amino acids. mTOR signaling regulates the phosphorylation of several proteins, the best characterized being ones that control mRNA translation. Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) undergoes phosphorylation at multiple sites. Here we show that amino acids regulate the N-terminal phosphorylation sites in 4E-BP1 through the RAIP motif in a rapamycin-insensitive manner. Several criteria indicate this reflects a rapamycin-insensitive output from mTOR. In contrast, the insulin-stimulated phosphorylation of the C-terminal site Ser64/65 is generally sensitive to rapamycin, as is phosphorylation of another well-characterized target for mTOR signaling, S6K1. Our data imply that it is unlikely that mTOR directly phosphorylates Thr69/70 in 4E-BP1. Although 4E-BP1 and S6K1 bind the mTOR partner, raptor, our data indicate that the outputs from mTOR to 4E-BP1 and S6K1 are distinct. In cells, efficient phosphorylation of 4E-BP1 requires it to be able to bind to eIF4E, whereas phosphorylation of 4E-BP1 by mTOR in vitro shows no such preference. These data have important implications for understanding signaling downstream of mTOR and the development of new strategies to impair mTOR signaling.
In vivo ultrasound real‐time motion of the cervical spine during intubation under manual in‐line stabilization: a comparison of intubation methods

Background and objective: In emergency trauma situations, manual in‐line stabilization of the cervical spine is recommended to reduce cervical spine movement during intubation. The aim of this study was to compare the effect of manual in‐line stabilization during different intubation techniques on three‐dimensional cervical spine movements and times to intubation. Methods: Forty‐eight subjects without any history of trauma, inflammatory or degenerative disorder of the cervical spine were randomly grouped, regardless of gender or age. All underwent elective surgery under general anaesthesia. Under manual in‐line stabilization, laryngeal intubation with Macintosh laryngoscope, intubating laryngeal mask airway, fibre‐endoscopic oral intubation and fibre‐endoscopic nasal intubation was performed. During the intubation process, cervical three‐dimensional motion was detected by an ultrasound real‐time motion analysis system and intubation times were measured. Results: Cervical spine range in the extension/flexion direction of orolaryngeal intubation with Macintosh (17.57 ± 8.23°) showed significantly more movement than using the intubating laryngeal mask airway (4.60 ± 1.51°) and fibreoptic procedures. Intubating laryngeal mask airway was significantly different than the fibreoptic intubation techniques. There was also a significant difference between oral (3.61 ± 2.25°) nasal and (5.88 ± 3.11°) fibreoptic intubation. Times to intubation all differed significantly (P < 0.05) for the Macintosh laryngoscope (27.25 ± 8.56 s) and for the intubating laryngeal mask airway (16.5 ± 9.76 s). Fibreendoscopic laryngoscopic oral (52.91 ± 56.27 s) and nasal (82.32 ± 54.06 s) intubation resulted in further prolongation of the times to intubation. Conclusions: The intubating laryngeal mask airway with manual in‐line stabilization is a potentially useful adjunct to intubation of patients with potential cervical spine injury, if there are no contraindications to these methods. These results predict that fibreoptic procedures may be a safe instrument for airway management in patients with potential cervical spine injuries; however, the main disadvantages are the longer intubation times.
Immunohistochemical pathology of the corneal endothelium in iridocorneal endothelial syndrome.

PURPOSE To evaluate immunohistochemical staining of the endothelia of corneas from patients with clinical diagnoses of iridocorneal endothelial (ICE) syndrome. METHODS Corneas diagnosed with ICE syndrome and removed during corneal transplantation were freshly frozen, sectioned, and stained with monoclonal antibodies to keratin subgroups, vimentin, desmin, and a series of other antibodies against intermediate filaments. Transmission electron microscopy was performed on segments of these corneas fixed in glutaraldehyde. RESULTS There was almost universal staining of the endothelial layer with A1 and A3 keratin monoclonal antibodies and vimentin. Transmission electron microscopy of the corneas also confirmed features consistent with keratin. CONCLUSIONS The "endothelial" cell layer in the iridocorneal endothelial syndrome has electron microscopic and immunohistochemical characteristics of epithelial-like cells, but it also cross-reacts with vimentin, suggesting that these cells retain or derive some endothelial staining characteristics as well. This "epithelialization" of the endothelial layer may explain the progressive cellular proliferation across angle and iris similar to that seen in iatrogenic epithelial downgrowth and posterior polymorphous endothelial dystrophy.
[Utilization of health service in women with reproductive tract infections in urban and rural areas].

OBJECTIVE To provide insight on psychosocial factors underlying utilization of health services of women whom perceived reproductive tract infection (RTI) symptoms. METHODS A cross-sectional study, adopted Aday and Andersen's Social Behaviour Model was conducted in 1998 - 1999 in China. Hebei province and Beijing were purposely chosen as the research sites. All eligible married women aged 21 to 60, 864 subjects, were interviewed in person. RESULTS Findings showed that the percentage of self-reported symptoms of RTIs was 35.6 in urban compared to 46.8 in the rural areas. The proportion of women with RTIs who utilized health services was 27.5 versus 26.7 percent among the two groups. Urban women, mostly 'white collar' class, with free medical service, satisfied with health providers, receiving information from health provider and having severe current experience RTIs, were more likely to use health services. Rural women, however, having both severe prior experience and current experience of RTIs, high family income, having much knowledge about self-medication, perceiving less social stigma of getting RTIs, and perceiving severity of RTIs, were more likely to use health services. CONCLUSION These findings showed that there was a great need on providing culturally acceptable reproductive health education at different places so as to improve women's ability of self-care. Regular medical check-up for women is also important for improving the quality of health service. Reform on health insurance seemed necessary. Factors as social stigma related to RTIs, giving women social and moral support also need to be taken into account.
Implementing Baby-Friendly Practices: Strategies for Success

AbstractBreastfeeding is widely viewed as the optimal feeding method for infants among professional nursing and medical organizations. Its health benefits have been comprehensively studied and documented for both infants and mothers. Hospitals and birthing centers can strongly influence the outcomes for mothers who choose to breastfeed by establishing effective breastfeeding behaviors immediately after birth and during the hospital stay. The Baby-Friendly USA initiative outlines 10 steps to successful breastfeeding. Although these steps have been successfully supported in practice, they can be difficult to implement due to a variety of factors, including resistance to change. Specific steps generate more barriers to overcome than others—namely exclusive breastfeeding without supplementation or pacifiers, rooming-in for 23 out of 24 hours, and skin-to-skin contact with a parent immediately after birth and during the hospital stay. Our hospital spent 5 years implementing Baby-Friendly practices to prepare for a successful site visit. In the process, barriers to key Baby-Friendly steps were overcome through creative approaches and strategic education for staff, physicians, and parents. The purpose of this article is to outline specific actions taken that assisted our hospital in its successful journey. Those actions and strategies will hopefully be of value to others in their journey toward designation.
Developing a Social Media Strategy: A Professional Association Perspective

Relationship engagement is the cornerstone of social media, hence the word “networking” in social networking sites. Social media sites can make excellent communications vehicles for many not-for-profits since building and maintaining relationships are fundamental to their existence. This social media strategy audit and case study examines the best practices for organizations, in particular, non-profit professional associations, and proposes a social media strategy for a national Canadian professional association. The study found that while many professional associations are using social media to engage with their members and other stakeholders, there are a number of key elements that need to be considered when associations develop social media strategies including: implementing a social media policy for staff and members; allocating proper staff resources, including training; tying social media activities back to the strategic plan of the organization; ensuring consistency of messages and content across platforms; and finally making sure social media activities are measured with both quantitative and qualitative measures.
Transfer learning for Diabetic Macular Edema (DME) detection on Optical Coherence Tomography (OCT) images

Diabetic Macular Edema (DME) is a common eye disease that causes irreversible vision loss for diabetic patients, if left untreated. Thus, early diagnosis of DME could help in early treatment and prevent blindness. This paper aims to create a framework based on deep learning for DME recognition on Spectral Domain Optical Coherence Tomography (SD-OCT) images through transfer learning. First, images are pre-processed: denoised using Block-Matching and 3-Dimension (BM3D) filtering and cropped through image boundary extraction. Later, features are extracted using CNN of AlexNet and finally images are classified using SVM classifier. The results are evaluated using 8-fold cross-validation. The experiments show that denoised and cropped images lead to better classification performances, exceeding previous other recent published works of 96% accuracy.
Analysis of extended Kalman filter based dynamic state estimator's performance under anomalous measurement conditions for power system

State estimation, at the center of the energy management system, is an important requirement for system monitoring. It leads to better control and stability of electric power system. Accurate state estimation at faster rate is a backbone for reliable operation of vastly complex electric power system. Phasor measurement unit based measurement system makes it feasible to feed measurement data to state estimator with high throughput and good accuracy. Hence, it is possible to predict states dynamically using dynamic state estimators. In literatures, the extended Kalman filter based dynamic state estimator is successfully employed under varying noise content in measurement and measurement data update rates. It is worthwhile to observe the tracking ability in a rare condition, when measurement data are unavailable to EKF based estimator algorithm for short duration. The paper investigates the EKF's tracking capability under such anomalous measurement conditions and result are deliberated.
Two-Dimensional Robust Magnetic Resonance Navigation of a Ferromagnetic Microrobot Using Pareto Optimality

This paper introduces a two-dimensional (2-D) autonomous navigation strategy of a 750-<inline-formula> <tex-math notation="LaTeX">${\mu \text{m}}$</tex-math></inline-formula> steel microrobot along a complex fluidic vascular network inside the bore of a clinical 3.0-T magnetic resonance imaging (MRI) scanner. To ensure successful magnetic resonance navigation of a microrobot along consecutive channels, the design of autonomous navigation strategy is needed, taking into account the major MRI technological constraints and physiological perturbations, e.g., nonnegligible pulsatile flow, limitations on the magnetic gradient amplitude, MRI overheating, and susceptibility artifacts uncertainties. An optimal navigation planning framework based on Pareto optimality is proposed in order to deal with this multiple-objective problem. Based on these optimal conditions, a dedicated control architecture has been implemented in an interventional medical platform for real-time propulsion, control, and imaging experiments. The reported experiments suggest that the likelihood of controlling autonomously untethered 750-<inline-formula> <tex-math notation="LaTeX">${\mu \text{m}}$</tex-math></inline-formula> magnetic microrobots is rendered possible in a complex 2-D centimeter-sized vascular phantom. The magnetic microrobot traveled intricate paths at a mean velocity of about 4 <inline-formula><tex-math notation="LaTeX">$\text{mms}^{-1}$</tex-math></inline-formula> with average tracking errors below 800 <inline-formula><tex-math notation="LaTeX">${\mu \text{m}}$</tex-math></inline-formula> with limited magnetic gradients <inline-formula><tex-math notation="LaTeX">$\pm \text{15}\ \text{mTm}^{-1}$</tex-math> </inline-formula>, which is compatible with clinical MRI scanners. The experiments demonstrate that it is effectively possible to autonomously guide a magnetic microrobot using a conventional MRI scanner with only a software upgrade.
Gene expression signatures differ with extent of atherosclerosis in monkey iliac artery

Objective:The aim of this study was to evaluate global gene expression patterns in the common iliac arteries of monkeys with a varied extent of atherosclerosis. Methods:The left common iliac artery was removed from ovariectomized cynomolgus monkeys (n = 12) after 6.5 years of consuming a diet containing fat and cholesterol at levels comparable with those consumed in Western populations. Arterial gene expression was analyzed using DNA microarray and real-time reverse transcription-polymerase chain reaction. Results:Significant differential expression of 986 genes was observed in iliac arteries containing moderate to large atherosclerotic plaques compared with normal/minimally affected reference group arteries. Atherosclerosis-associated genes included cytokines, chemokines, components of signal transduction pathways, and transcriptional activators and repressors, as well as other functional categories. Real-time reverse transcription-polymerase chain reaction confirmed a differential expression of genes chosen from a variety of functional categories. Specifically, the expression of genes for estrogen receptor-1, claudin 11, and brain heart protocadherin 7 was reduced, whereas the expression of genes for apolipoprotein E, growth differentiation factor 15, superoxide dismutase-2, SET domain bifurcated 2, phospholipase A2 group IIA, phospholipase A2 group VII, and ring finger protein 149 was increased in atherosclerotic arteries. Conclusions:The gene expression environment in arteries containing atherosclerotic plaques is profoundly different from that of relatively unaffected arteries and reflects the cellular and molecular complexity of atherosclerosis and associated arterial remodeling processes.
Market activity and price impact throughout time scales

This thesis tackles several issues raised by the multi-scale properties of financial data. It consists of four connected parts which can however be read independently. In the first part, we introduce the Rough Fractional Stochastic Volatility (RFSV) model. In this framework, the logarithm of the volatility is a fractional Ornstein-Uhlenbeck process with long mean reversion time scale and small Hurst index. We show that this model reproduces numer- ous stylized facts of financial data such as implied volatility properties, the autocorrelation structure and the regularity of the volatility. In particular, the RFSV sheds some new light on the supposed long memory property of volatility. The second part deals with the long-time behavior of Hawkes and autoregressive processes which are nearly unstable, that is whose kernels have a norm close to one. We show that in the case where the kernel has a light tail, nearly unstable Hawkes processes asymptotically behaves as integrated Cox-Ingersoll-Ross (CIR) processes. In the case where it has a power law shape, depending on the power law exponent, the limiting process asymptotically exhibits either long memory or a rough behavior. This enables us to use the modeling of the order flow as a Hawkes process to obtain a microstructural foundation of the rough nature of volatility. Similar results are obtained for autoregressive processes. In the third part of this thesis, we propose two estimation procedures for the kernels of Hawkes processes. These algorithms are in particular relevant to the case of slowly decreasing Hawkes kernels which corresponds to what is observed on financial data. The first method relies on the inversion of the Wiener-Hopf equation while the second is based on a likelihood maximization via a stochastic gradient ascent. Finally, we are interested in deriving, under very general assumptions, consequences of market efficiency on the structure of price impact. We prove the existence of a model independent fair price with respect to which the average ex post gain of limit orders must be equal to zero. We finally show that, under a few additional assumptions, price impact must be proportional to the market anticipation of the order flow imbalance.
Endogenous apolipoprotein A‐I stabilizes ATP‐binding cassette transporter A1 and modulates Toll‐like receptor 4 signaling in human macrophages

Apolipoprotein A‐I (ApoA‐I) is the main functional protein component of human high‐density lipoproteins. ApoA‐I shows various anti‐inflammatory and atheroprotective properties toward macrophages; however, endogenous apoA‐I expression has not been investigated in macrophages. We have shown that endogenous apoA‐I gene is expressed in human macrophages at both mRNA and protein levels. Endogenous ApoA‐I is localized in intracellular vesicles and at the external side of the plasma membrane in association with ATP‐binding cassette transporter A1 (ABCA1) and lipid rafts in macrophages. We have shown that endogenous ApoA‐I stabilizes ABCA1, moreover, down‐regulation of ApoA‐I by siRNA results in an increase of Toll‐like receptor 4 (TLR4) mRNA and membrane surface protein expression, as well as an enhancement of bacterial lipopolysaccharide (LPS)‐induced expression of tumor necrosis factor‐α (TNF‐α), interleukin 1β (IL‐1β), and inducible nitric oxide synthase (NOS2) genes in human macrophages. TNF‐α stimulates ApoA‐I expression and secretion (1.2±0.2 vs. 4.3±0.9 ng/mg total protein) in macrophages. Obtained results suggest that endogenous ApoA‐I has anti‐inflammatory properties, presumably due to ABCA1 stabilization in macrophages; these results elucidate the cell type‐specific mechanism of the TNF‐α‐mediated regulation of apoA‐I gene expression in monocytes and macrophages. —Mogilenko, D. A. , Orlov, S. V. , Trulioff, A. S. , Ivanov, A. V. , Nagumanov, V. K. , Kudriavtsev, I. V. , Shavva, V. S. , Tanyanskiy, D. A. , Perevozchikov, A. P. Endogenous apolipoprotein A‐I stabilizes ATP‐binding cassette transporter A1 and modulates Toll‐like receptor 4 signaling in human macrophages. FASEB J. 26, 2019‐2030 (2012). www.fasebj. org
Smoking and risk of rheumatoid arthritis.

OBJECTIVE To investigate smoking for its association with the incidence of seropositive and seronegative rheumatoid arthritis (RA). METHODS A cohort of adult Finns was examined by the Social Insurance Institution's Mobile Clinic in 1966-72. The 24,445 women and 28,364 men who had neither arthritis nor a history of it at the start of the study were followed until the end of 1989 using record linkage with the Institution's population register to identify patients entitled to free antirheumatic medication. Sufficient information was obtained on 512 incident cases of RA, of whom 119 men and 229 women were seropositive and 42 men and 122 women seronegative. RESULTS There was a close association between smoking and the incidence of seropositive RA in men. It was not due to confounding by age, geographical location of residence, marital status, social class, self-perceived general health, or body mass index, although these factors correlated with smoking history. As adjusted for these factors, the relative risk of seropositive RA was 2.6 (95% confidence interval, 1.3-5.3) in male ex-smokers and 3.8 (95% confidence interval, 2.0-6.9) in current smokers, in comparison with the men who had never smoked. The association persisted throughout the entire followup period, but it was most distinct after the first 14 years of followup. Smoking did not predict seropositive RA in women, nor was it predictive of seronegative RA in men or women. CONCLUSION Exposure to tobacco smoke, or some factor or cluster of factors associated with smoking, may trigger the production of rheumatoid factors and, in interaction with the male sex, subsequently contribute to the development of clinically manifest RA.