Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of Eye Movements in Mice

Background The mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum’s role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult. Methods We developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye’s angular velocity around the axis of eye rotation. Results When mice were rotated at 0.5 Hz and 2.5 Hz around the earth’s vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz. Conclusions To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.
A molecular and preclinical comparison of the PD-1–targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab

T-cell checkpoint inhibition has a profound impact on cancer care and the programmed cell death protein 1 (PD-1)–targeted antibodies nivolumab and pembrolizumab have been two of the lead molecules of this therapeutic revolution. Their clinical comparability is a highly relevant topic of discussion, but to a significant degree is a consequence of their molecular properties. Here we provide a molecular, preclinical, and early clinical comparison of the two antibodies, based on the available data and recent literature. We acknowledge the limitations of such comparisons, but suggest that based on the available data, differences in clinical trial outcomes between nivolumab and pembrolizumab are more likely drug-independent than drug-dependent.
PBHMDA: Path-Based Human Microbe-Disease Association Prediction

With the advance of sequencing technology and microbiology, the microorganisms have been found to be closely related to various important human diseases. The increasing identification of human microbe-disease associations offers important insights into the underlying disease mechanism understanding from the perspective of human microbes, which are greatly helpful for investigating pathogenesis, promoting early diagnosis and improving precision medicine. However, the current knowledge in this domain is still limited and far from complete. Here, we present the computational model of Path-Based Human Microbe-Disease Association prediction (PBHMDA) based on the integration of known microbe-disease associations and the Gaussian interaction profile kernel similarity for microbes and diseases. A special depth-first search algorithm was implemented to traverse all possible paths between microbes and diseases for inferring the most possible disease-related microbes. As a result, PBHMDA obtained a reliable prediction performance with AUCs (The area under ROC curve) of 0.9169 and 0.8767 in the frameworks of both global and local leave-one-out cross validations, respectively. Based on 5-fold cross validation, average AUCs of 0.9082 ± 0.0061 further demonstrated the efficiency of the proposed model. For the case studies of liver cirrhosis, type 1 diabetes, and asthma, 9, 7, and 9 out of predicted microbes in the top 10 have been confirmed by previously published experimental literatures, respectively. We have publicly released the prioritized microbe-disease associations, which may help to select the most potential pairs for further guiding the experimental confirmation. In conclusion, PBHMDA may have potential to boost the discovery of novel microbe-disease associations and aid future research efforts toward microbe involvement in human disease mechanism. The code and data of PBHMDA is freely available at http://www.escience. cn/system/file? fileId=85214.
Multiclass Cancer Classification by Using Fuzzy Support Vector Machine and Binary Decision Tree With Gene Selection

We investigate the problems of multiclass cancer classification with gene selection from gene expression data. Two different constructed multiclass classifiers with gene selection are proposed, which are fuzzy support vector machine (FSVM) with gene selection and binary classification tree based on SVM with gene selection. Using F test and recursive feature elimination based on SVM as gene selection methods, binary classification tree based on SVM with F test, binary classification tree based on SVM with recursive feature elimination based on SVM, and FSVM with recursive feature elimination based on SVM are tested in our experiments. To accelerate computation, preselecting the strongest genes is also used. The proposed techniques are applied to analyze breast cancer data, small round blue-cell tumors, and acute leukemia data. Compared to existing multiclass cancer classifiers and binary classification tree based on SVM with F test or binary classification tree based on SVM with recursive feature elimination based on SVM mentioned in this paper, FSVM based on recursive feature elimination based on SVM can find most important genes that affect certain types of cancer with high recognition accuracy.
Enhanced Interhemispheric Functional Connectivity Compensates for Anatomical Connection Damages in Subcortical Stroke

Background and Purpose— Motor recovery after stroke has been shown to be correlated with both the fractional anisotropy (FA) of the affected corticospinal tract (CST) and the interhemispheric resting-state functional connectivity (rsFC) of the primary motor cortex (M1). However, the role of the restoration or enhancement of the M1–M1 rsFC in motor recovery remains largely unknown. We aimed to clarify this issue by investigating the correlations between the M1–M1 rsFC and the integrity of the M1–M1 anatomic connection and the affected CST in chronic subcortical stroke patients with good motor outcomes. Methods— Twenty patients and 16 healthy controls underwent multimodal magnetic resonance imaging examinations. Diffusion tensor imaging was used to reconstruct the M1–M1 anatomic connection and bilateral CSTs. White matter integrity of these tracts was assessed using FA. Resting-state functional magnetic resonance imaging was used to calculate M1–M1 rsFC. Group differences in these measures were compared. Correlations between M1–M1 rsFC and FA of the M1–M1 anatomic connection and the affected CST were analyzed in patients with stroke. Results— Compared with healthy controls, patients with stroke exhibited significantly reduced FA in the affected CST and the M1–M1 anatomic connection and a significantly increased M1–M1 rsFC. The FA values of the affected CST were positively correlated with the M1–M1 anatomic connection, and these FA values were negatively correlated with the M1–M1 rsFC in these patients. Conclusions— Our findings suggest that the M1–M1 anatomic connection impairment is secondary to CST damage, and the M1–M1 rsFC enhancement may reflect compensatory or reactive neural plasticity in stroke patients with CST impairment.
Effect of Ginger Supplementation on Proinflammatory Cytokines in Older Patients with Osteoarthritis: Outcomes of a Randomized Controlled Clinical Trial

ABSTRACT There is limited evidence that ginger powder consumption can relieve pain and inflammation due to specific anti-inflammatory phytochemical constitutents. This study investigates the effect of ginger supplementation on proinflammatory factors in participants (n = 120) of a randomized double-blind placebo-controlled 3-month clinical trial investigating knee osteoarthritis. Patients were randomly assigned to one of two groups: the ginger group (GG) or the placebo group (PG). Administered daily for 3 months, participants in the GG intervention received capsules containing 500 mg of ginger powder, while PG participants received capsules filled with 500 mg starch. Serum samples collected at baseline and 3 months were analyzed for serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). At baseline, proinflammatory cytokine concentrations did not differ by group. However, at 3 months, both cytokines decreased in the GG relative to the PG. The results of this study indicate that ginger supplementation may have a promising benefits for knee osteoarthritis and may, therefore, may warrant further study.
Membranoproliferative Glomerulonephritis Type I in Renal Transplantation Patients: A Single-Center Study of a Cohort of 68 Renal Transplants Followed Up for 11 Years

Background. To evaluate the long-term outcome of renal transplant patients with membranoproliferative glomerulonephritis (MPGN) type I and the impact of recurrence. Methods. The outcomes of 68 renal transplants performed between 1976 and 2009 in 63 patients with MPGN were compared with those of 136 controls matched for time of transplantation, sex, age, and source of donors. Results. The mean posttransplant follow-up was 131.3±83.8 months for patients with MPGN and 139.21±88.7 months for controls. At 15 years, patient survival rates were 76.2% in patients with MPGN and 78.8% in controls (P=ns), whereas pure graft survival rates were 68% in MPGN and 67.9% in controls (P=ns). MPGN recurred in 16 patients (23.5%) 44±30.3 months after transplant (range, 3.5–105 months). Of recurrent grafts, nine were lost for recurrence within 116.5±51.36 months, three patients died with functioning kidney, the other 4 grafts are functioning 156.7±47.5 months after transplantation. Graft survival at 15 years was 73.5% in nonrecurrent and 40.4% in recurrent patients (P=0.02). Patients with recurrence were younger at diagnosis of MPGN (17.64±5.02 years vs. 22.9±9.6 years; P=0.037) and had low C3 more frequently than nonrecurrent patients (75% vs. 28.8%; P=0.01). Proteinuria was higher in recurrent patients who lost the graft in comparison with those with functioning graft (7.14±4.05 vs. 2.86±1.95; P=0.02). Conclusions. The long-term patient and graft survival were similar in patients with MPGN and in controls. Recurrence occurred in one-fourth of patients and caused graft loss in 56%. Younger age at diagnosis of MPGN and low C3 during transplantation seems to be predictive of recurrence.
Branched Lateral Tail Fiber Organization in T5-Like Bacteriophages DT57C and DT571/2 is Revealed by Genetic and Functional Analysis

The T5-like siphoviruses DT57C and DT571/2, isolated from horse feces, are very closely related to each other, and most of their structural proteins are also nearly identical to T5 phage. Their LTFs (L-shaped tail fibers), however, are composed of two proteins, LtfA and LtfB, instead of the single Ltf of bacteriophage T5. In silico and mutant analysis suggests a possible branched structure of DT57C and DT571/2 LTFs, where the LtfB protein is connected to the phage tail via the LtfA protein and with both proteins carrying receptor recognition domains. Such adhesin arrangement has not been previously recognized in siphoviruses. The LtfA proteins of our phages are found to recognize different host O-antigen types: E. coli O22-like for DT57C phage and E. coli O87 for DT571/2. LtfB proteins are identical in both phages and recognize another host receptor, most probably lipopolysaccharide (LPS) of E. coli O81 type. In these two bacteriophages, LTF function is essential to penetrate the shield of the host’s O-antigens. We also demonstrate that LTF-mediated adsorption becomes superfluous when the non-specific cell protection by O-antigen is missing, allowing the phages to bind directly to their common secondary receptor, the outer membrane protein BtuB. The LTF independent adsorption was also demonstrated on an O22-like host mutant missing O-antigen O-acetylation, thus showing the biological value of this O-antigen modification for cell protection against phages.
Temporally Regulated Traffic of HuR and Its Associated ARE-Containing mRNAs from the Chromatoid Body to Polysomes during Mouse Spermatogenesis

Background In mammals, a temporal disconnection between mRNA transcription and protein synthesis occurs during late steps of germ cell differentiation, in contrast to most somatic tissues where transcription and translation are closely linked. Indeed, during late stages of spermatogenesis, protein synthesis relies on the appropriate storage of translationally inactive mRNAs in transcriptionally silent spermatids. The factors and cellular compartments regulating mRNA storage and the timing of their translation are still poorly understood. The chromatoid body (CB), that shares components with the P. bodies found in somatic cells, has recently been proposed to be a site of mRNA processing. Here, we describe a new component of the CB, the RNA binding protein HuR, known in somatic cells to control the stability/translation of AU-rich containing mRNAs (ARE-mRNAs). Methodology/Principal Findings Using a combination of cell imagery and sucrose gradient fractionation, we show that HuR localization is highly dynamic during spermatid differentiation. First, in early round spermatids, HuR colocalizes with the Mouse Vasa Homolog, MVH, a marker of the CB. As spermatids differentiate, HuR exits the CB and concomitantly associates with polysomes. Using computational analyses, we identified two testis ARE-containing mRNAs, Brd2 and GCNF that are bound by HuR and MVH. We show that these target ARE-mRNAs follow HuR trafficking, accumulating successively in the CB, where they are translationally silent, and in polysomes during spermatid differentiation. Conclusions/Significance Our results reveal a temporal regulation of HuR trafficking together with its target mRNAs from the CB to polysomes as spermatids differentiate. They strongly suggest that through the transport of ARE-mRNAs from the CB to polysomes, HuR controls the appropriate timing of ARE-mRNA translation. HuR might represent a major post-transcriptional regulator, by promoting mRNA storage and then translation, during male germ cell differentiation.
Effects of Ranolazine on Disease-Specific Health Status and Quality of Life Among Patients With Acute Coronary Syndromes: Results from the MERLIN-TIMI 36 Randomized Trial

Background—Ranolazine has been shown to reduce myocardial ischemia and symptom severity among selected patients with chronic angina. However, data regarding the effect of ranolazine on health status/quality of life (QOL) are limited. Methods and Results—We performed a prospective QOL analysis alongside the Metabolic Efficiency with Ranolazine for Less Ischemia in Non–ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial, a randomized, double-blind, placebo-controlled trial of ranolazine in 6560 patients with non–ST-elevation acute coronary syndromes. Health status/QOL was evaluated at baseline and 4, 8, and 12 months after index hospitalization using the Seattle Angina Questionnaire, Rose dyspnea scale, SF-12, and EuroQol-5D. Health status/QOL scores improved significantly at all follow-up time points for both treatment arms. In the overall population, randomization to ranolazine was associated with minimal 12-month improvements in angina frequency and Seattle Angina Questionnaire-QOL (P<0.05). In subsequent exploratory analyses, there was a significant interaction between the benefits of ranolazine and anginal status before the index event. Among patients with prior angina (n=3565), treatment with ranolazine was associated with modest benefits across the full range of QOL domains, with the greatest benefits observed in angina frequency (mean effect=3.4; P<0.001) and Seattle Angina Questionnaire-QOL (mean effect=2.7; P<0.001). There were no significant benefits among patients without prior angina, however. Conclusion—Among a broad population of patients with unstable coronary disease, ranolazine had a minimal effect on disease-specific health status and QOL over ≈12 months of follow-up. Posthoc subgroup analysis, however, suggested a modest benefit among the subgroup of patients with angina before their acute coronary syndromes event.
Photoacoustic imaging of tumor targeting with riboflavin-functionalized theranostic nanocarriers

Photoacoustic imaging is an emerging method in the molecular imaging field, providing high spatiotemporal resolution and sufficient imaging depths for many clinical applications. Therefore, the aim of this study was to use photoacoustic imaging as a tool to evaluate a riboflavin (RF)-based targeted nanoplatform. RF is internalized by the cells through a specific pathway, and its derivatives were recently shown as promising tumor-targeting vectors for the drug delivery systems. Here, the RF amphiphile synthesized from a PEGylated phospholipid was successfully inserted into a long-circulating liposome formulation labeled with the clinically approved photoacoustic contrast agent – indocyanine green (ICG). The obtained liposomes had a diameter of 124 nm (polydispersity index =0.17) and had a negative zeta potential of −26 mV. Studies in biological phantoms indicated a stable and concentration-dependent photoacoustic signal (Vevo® LAZR) of the ICG-containing RF-functionalized liposomes. In A431 cells, a high uptake of RF-functionalized liposomes was found and could be blocked competitively. First, studies in mice revealed ~3 times higher photoacoustic signal in subcutaneous A431 tumor xenografts (P<0.05) after injection of RF-functionalized liposomes compared to control particles. In this context, the application of a spectral unmixing protocol confirmed the initial quantitative data and improved the localization of liposomes in the tumor. In conclusion, the synthesized RF amphiphile leads to efficient liposomal tumor targeting and can be favorably detected by photoacoustic imaging with a perspective of theranostic applications.
Multi-input multi-output fading channel tracking and equalization using Kalman estimation

This paper addresses the problem of channel tracking and equalization for multi-input multi-output (MIMO) time-varying frequency-selective channels. These channels model the effects of inter-symbol interference (ISI), co-channel interference (CCI), and noise. A low-order autoregressive model approximates the MIMO channel variation and facilitates tracking via a Kalman filter. Hard decisions to aid Kalman tracking come from a MIMO finite-length minimum-mean-squared-error decision-feedback equalizer (MMSE-DFE), which performs the equalization task. Since the optimum DFE for a wide range of channels produces decisions with a delay /spl Delta/ > 0, the Kalman filter tracks the channel with a delay. A channel prediction module bridges the time gap between the channel estimates produced by the Kalman filter and those needed for the DFE adaptation. The proposed algorithm offers good tracking behavior for multiuser fading ISI channels at the expense of higher complexity than conventional adaptive algorithms. Applications include synchronous multiuser detection of independent transmitters, as well as coordinated transmission through many transmitter/receiver antennas, for increased data rate.
802.11ec: Collision Avoidance Without Control Messages

In this paper, we design, implement, and evaluate 802.11ec (Encoded Control), an 802.11-based protocol without control messages: Instead, 802.11ec employs correlatable symbol sequences that, together with the timing the codes are transmitted, encode all control information and change the fundamental design properties of the MAC. The use of correlatable symbol sequences provides two key advantages: 1) efficiency, as it permits a near order of magnitude reduction of the control time; 2) robustness, because codes are short and easily detectable even at low signal-to-interference-plus-noise ratio (SINR) and even while a neighbor is transmitting data. We implement 802.11ec on a field programmable gate array (FPGA)-based software defined radio. We perform a large number of experiments and show that, compared to 802.11 (with and without RTS/CTS), 802.11ec achieves a vast efficiency gain in conveying control information and resolves key throughput and fairness problems in the presence of hidden terminals, asymmetric topologies, and general multihop topologies.
Optimal implementation of conjunctive queries in relational data bases

We define the class of conjunctive queries in relational data bases, and the generalized join operator on relations. The generalized join plays an important part in answering conjunctive queries, and it can be implemented using matrix multiplication. It is shown that while answering conjunctive queries is NP complete (general queries are PSPACE complete), one can find an implementation that is within a constant of optimal. The main lemma used to show this is that each conjunctive query has a unique minimal equivalent query (much like minimal finite automata).
Inflammaging: disturbed interplay between autophagy and inflammasomes

Inflammaging refers to a low-grade pro-inflammatory phenotype which accompanies aging in mammals. The aging process is associated with a decline in autophagic capacity which impairs cellular housekeeping, leading to protein aggregation and accumulation of dysfunctional mitochondria which provoke reactive oxygen species (ROS) production and oxidative stress. Recent studies have clearly indicated that the ROS production induced by damaged mitochondria can stimulate intracellular danger-sensing multiprotein platforms called inflammasomes. Nod-like receptor 3 (NLRP3) can be activated by many danger signals, e.g. ROS, cathepsin B released from destabilized lysosomes and aggregated proteins, all of which evoke cellular stress and are involved in the aging process. NLRP3 activation is also enhanced in many age-related diseases, e.g. atherosclerosis, obesity and type 2 diabetes. NLRP3 activates inflammatory caspases, mostly caspase-1, which cleave the inactive precursors of IL-1β and IL-18 and stimulate their secretion. Consequently, these cytokines provoke inflammatory responses and accelerate the aging process by inhibiting autophagy. In conclusion, inhibition of autophagic capacity with aging generates the inflammaging condition via the activation of inflammasomes, in particular NLRP3. We will provide here a perspective on the current research of the ROS-dependent activation of inflammasomes triggered by the decline in autophagic cleansing of dysfunctional mitochondria.
Electronic commerce-enabled supply chain process integration and business value

Purpose – The purpose of this paper is to develop and test a model to analyze the relationships between three aspects of technical electronic commerce (EC)‐based information system (IS) resources; the supply chain process integration; and business value.Design/methodology/approach – The paper is consistent with the perspective on IS‐enabled organizational capabilities and resource based view of the firm. A questionnaire‐based survey was conducted to collect data from 214 supply chain, logistics, or procurement/purchasing managers of leading manufacturing firms.Findings – The findings suggest that supply chain process integration, a key EC‐enabled organizational capability, can enhance business value. We found that this capability serve as a catalyst in transforming technical EC‐based IS resources (technical quality of EC applications, EC advancements, and EC alignment) into higher value for a firm.Research limitations/implications – Among other limitations, this paper does not address human IS resources a.