Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation and Applications of Human Pluripotent Stem Cells Induced into Neural Lineages and Neural Tissues

Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern medicine, now the focus of many researchers and media outlets. The hype is well-earned because of the potential of stem cells to contribute to disease modeling, drug screening, and even therapeutic approaches. In this review, we focus first on neural differentiation of these cells. In a second part we compare the various cell types available and their advantages for in vitro modeling. Then we provide a “state-of-the-art” report about two major biomedical applications: (1) the drug and toxicity screening and (2) the neural tissue replacement. Finally, we made an overview about current biomedical research using differentiated hPSCs.
Protein Engineering of Toluene-o-Xylene Monooxygenase from Pseudomonas stutzeri OX1 for Synthesizing 4-Methylresorcinol, Methylhydroquinone, and Pyrogallol

ABSTRACT Toluene-o-xylene monooxygenase (ToMO) from Pseudomonas stutzeri OX1 oxidizes toluene to 3- and 4-methylcatechol and oxidizes benzene to form phenol; in this study ToMO was found to also form catechol and 1,2,3-trihydroxybenzene (1,2,3-THB) from phenol. To synthesize novel dihydroxy and trihydroxy derivatives of benzene and toluene, DNA shuffling of the alpha-hydroxylase fragment of ToMO (TouA) and saturation mutagenesis of the TouA active site residues I100, Q141, T201, and F205 were used to generate random mutants. The mutants were initially identified by screening with a rapid agar plate assay and then were examined further by high-performance liquid chromatography and gas chromatography. Several regiospecific mutants with high rates of activity were identified; for example, Escherichia coli TG1/pBS(Kan)ToMO expressing the F205G TouA saturation mutagenesis variant formed 4-methylresorcinol (0.78 nmol/min/mg of protein), 3-methylcatechol (0.25 nmol/min/mg of protein), and methylhydroquinone (0.088 nmol/min/mg of protein) from o-cresol, whereas wild-type ToMO formed only 3-methylcatechol (1.1 nmol/min/mg of protein). From o-cresol, the I100Q saturation mutagenesis mutant and the M180T/E284G DNA shuffling mutant formed methylhydroquinone (0.50 and 0.19 nmol/min/mg of protein, respectively) and 3-methylcatechol (0.49 and 1.5 nmol/min/mg of protein, respectively). The F205G mutant formed catechol (0.52 nmol/min/mg of protein), resorcinol (0.090 nmol/min/mg of protein), and hydroquinone (0.070 nmol/min/mg of protein) from phenol, whereas wild-type ToMO formed only catechol (1.5 nmol/min/mg of protein). Both the I100Q mutant and the M180T/E284G mutant formed hydroquinone (1.2 and 0.040 nmol/min/mg of protein, respectively) and catechol (0.28 and 2.0 nmol/min/mg of protein, respectively) from phenol. Dihydroxybenzenes were further oxidized to trihydroxybenzenes with different regiospecificities; for example, the I100Q mutant formed 1,2,4-THB from catechol, whereas wild-type ToMO formed 1,2,3-THB (pyrogallol). Regiospecific oxidation of the natural substrate toluene was also checked; for example, the I100Q mutant formed 22% o-cresol, 44% m-cresol, and 34% p-cresol, whereas wild-type ToMO formed 32% o-cresol, 21% m-cresol, and 47% p-cresol.
The Cut-and-Enhance Method: Selecting Clusters of Galaxies from the Sloan Digital Sky Survey Commissioning Data

We describe an automated method, the cut-and-enhance (CE) method, for detecting clusters of galaxies in multicolor optical imaging surveys. This method uses simple color cuts, combined with a density enhancement algorithm, to up-weight pairs of galaxies that are close in both angular separation and color. The method is semiparametric, since it uses minimal assumptions about cluster properties in order to minimize possible biases. No assumptions are made about the shape of clusters, their radial profile, or their luminosity function. The method is successful in finding systems ranging from poor to rich clusters of galaxies, of both regular and irregular shape. We determine the selection function of the CE method via extensive Monte Carlo simulations that use both the real, observed background of galaxies and a randomized background of galaxies. We use position-shuffled and color-shuffled data to perform false-positive tests. We have also visually checked all the clusters detected by the CE method. We apply the CE method to the 350 deg2 of the Sloan Digital Sky Survey (SDSS) commissioning data and construct an SDSS CE galaxy cluster catalog with an estimated redshift and richness for each cluster. The CE method is compared with other cluster selection methods used on SDSS data such as the matched filter, "maxBCG," and Voronoi tessellation techniques. The CE method can be adopted for cluster selection in any multicolor imaging survey.
In vitro susceptibilities of Chlamydia pneumoniae (Chlamydia sp. strain TWAR)

The in vitro susceptibilities of two clinical isolates of Chlamydia pneumoniae from Brooklyn, N.Y. , were determined for tetracycline, erythromycin, sulfamethoxazole, ciprofloxacin, and three new macrolides--azithromycin, clarithromycin, and roxithromycin. Clarithromycin was the most active drug tested, followed by the other macrolides, tetracycline, and ciprofloxacin.
The Ring Array Processor ( RAP ) : Algorithms and Architecture

In our speech recognition research, we have been experimenting with layered "neural" algorithms as probabilistic estimators for a Hidden Markov Model (HMM) procedure [1]-[3]. Features representing the spectral content of the speech are estimated 100 times per second. A layered network is trained to predict the phonetic label of each 10 msec "frame". This network takes as its input the spectral features from one or more frames, and has an output layer consisting of one unit per phonetic category. For some of our experiments, the input is continuous, and hidden layers are used. For others, the speech features are vector-quantized to map the frame into one of a set of prototype vectors, and the network input consists of a binary input neuron for each possible feature value, only one of which can be active at a time. In either case, the neural network is trained by back-propagation [4][5], augmented by a generalization-based stopping criterion [6]. It can be shown [7] that when the output targets are coded as 1 for the correct class and 0 for the others, and when a sum-of-squares error criterion is used, the trained output values are estimates of Maximum A Posteriori (MAP) probabilities, i.e. the probability of each class given the input features. This proof also is valid for some other common error criteria, such as relative entropy. When divided by the prior probabilities for each class, these values are proportional to the likelihoods which can be used as emission probabilities in the Viterbi decoding step of an HMM speech recognizer. A network can be useful for this procedure because it can estimate joint probabilities (joint over multiple features or time frames) without strong assumptions about the independence or parametric relation of the separate dimensions. We hav e conducted a number of experiments which seem to confirm the utility of this approach.
Preferential In Situ CD4+CD56+ T Cell Activation and Expansion within Human Glioblastoma

Recent evidence suggests that suppression of the cellular immune response is often attributable to populations of functionally distinct T cells that act to down-regulate Ag-specific effector T cells. Using flow cytometry, we evaluated tumor-infiltrating lymphocytes (TIL) from patients undergoing neurosurgical resection of glioblastoma multiforme (GBM), metastatic lung carcinoma, and meningioma for markers known to be expressed on immunoregulatory T cells. Ex vivo phenotypic characteristics, cellular proliferation, and cytokine expression patterns were compared between T cell subsets found in the PBMC and within TIL from fresh tumor samples. Interestingly, nearly half of all T cells infiltrating GBM specimens were CD56+ T cells, while much smaller percentages of similar cells were identified within metastatic lung tumors and meningiomas. CD56+ T cells identified within GBM were not canonical, or “invariant,” NKT cells, as they demonstrated diverse TCR expression, a primarily CD4 single-positive phenotype, and lack of CD1d reactivity. The percentage of CD56+ T cells exhibiting evidence of proliferation within GBM was 3- to 4-fold higher than the proportion of proliferating CD56− T cells from these lesions. In addition, direct ex vivo analysis of cytokine expression by TIL from GBM demonstrated significant numbers of IL-4/IL-13 positive cells, cytokines that are integral in the cell-mediated repression of tumor immunity in experimental models. We propose that GBM has a unique capacity to recruit and activate CD4+CD56+ T cells, a population that has not been previously described within human tumors.
Basal keratinocyte tetrasomy in low-grade squamous intra-epithelial lesions of the cervix is restricted to high and intermediate risk HPV infection but is not type-specific

Human papillomavirus (HPV) infection appears to be an early event in cervical carcinogenesis with additional abnormalities being required for biological transformation. We have analysed 179 low-grade cervical squamous intra-epithelial lesions (SILs) and 15 normal cervices for the presence of HPV using both in situ hybridization and polymerase chain reaction (PCR). PCR was performed with GP5+/GP6+ primers followed by hybridization using probes for low (HPV 6, 11, 40, 42, 43, 44), intermediate (HPV 31, 33, 35, 39, 51, 52, 58, 59, 66 and 68) and high-risk HPVs (HPV 16, 18, 45 and 56). Interphase cytogenetic analysis using pericentromeric probes for chromosomes 1, 3, 4, 6, 10, 11, 17, 18 and X was also performed to identify numerical chromosomal abnormalities. Tetrasomy of all nine chromosomes was identified within basal keratinocytes, was restricted to epithelia infected with high risk (17 of 46) or intermediate risk (23 of 83) HPVs but was not HPV type-specific. Tetrasomy was not identified in any of the epithelia infected with low risk HPVs (n = 62). These numbers include multiple infection. These findings indicate that the induction of tetrasomy is a property restricted to high and intermediate-risk HPV types but that it is not type-specific. The factors governing which lesions will develop this abnormality are as yet unclear. © 2000 Cancer Research Campaign
Genetic relatedness as a determinant of predisposition to Ascaris lumbricoides and Trichuris trichiura infection

SUMMARY The present study examines the role of host genetics in predisposition to Ascaris lumbricoides and Trichuris trichiura infection, by comparing the associations between age-standardized infection intensities of parents and their children (genetically related), with age-standardized infection intensities of parents alone (not related), within families previously demonstrated to exhibit familial predisposition. The lack of a consistent trend in infection intensity associations within families, in particular the lack of a stronger association between parents and their children than between unrelated parents, suggests that host genetic factors are not a major determinant of infection status. If there is a genetic basis for predisposition, then the data suggest that the effects of this genetic basis are overwhelmed by other, environmental or behavioural features of the family household.
Estimation of soil organic carbon, nitrogen, and phosphorus losses induced by wind erosion in Northern China

The loss of nutrients induced by wind erosion causes serious land degradation. Northern China suffers from severe wind erosion that causes massive amounts of soil nutrients to be lost and results in land degradation. To thoroughly comprehend the mechanisms of land degradation in Northern China, the spatiotemporal distribution of nutrients losses induced by wind erosion must be considered. Therefore, in this study, a wind erosion model was employed to obtain the PM10 emissions in Northern China from 2001 to 2014, and the quantities of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) entrained by PM10 were obtained using the integrated soil database of China. The results showed that the losses of SOC, TN, and TP induced by wind erosion were 0.894, 0.184, and 0.123 Tg/a, respectively, and the spatial distributions of these three nutrients differed from one another. According to the Moderate Resolution Imaging Spectroradiometer land‐cover data, the nutrients lost from desert ecosystems contributed the largest fractions of the total nutrients lost in Northern China, and the fractions of SOC, TN, and TP losses from the desert ecosystems all exceeded 50%. Following the desert ecosystems, the grassland ecosystems also had higher fractions of nutrients losses. The farmland ecosystems, which were the most severely impacted by human activities, contributed to less than 10% of the total nutrients losses.
Achieving High-Throughput State Machine Replication in Multi-core Systems

The traditional architecture used by implementations of Replicated State Machines (RSM) does not fully exploit modern multi-core CPUs. This is increasingly the limiting factor in their performance, because network speeds are increasing much faster than the single-thread performance of CPUs. Thus, when deployed on Gigabit-class networks and exposed to a workload of small to medium size client requests, RSMs are often CPU-bound, as they are only able to leverage a few cores, even though many more may be available. In this work, we revisit the traditional architecture of a RSM implementation, showing how it can be parallelized so that its performance scales with the number of cores in the nodes. We do so by applying several good practices of concurrent programming to the specific case of state machine replication, including staged execution, workload partitioning, actors, and non-blocking data structures. We describe and test a Java prototype of our architecture, based on the Paxos protocol. With a workload consisting of small requests, we achieve a six times improvement in throughput using eight cores. More generally, in all our experiments we have consistently reached the limits of the network subsystem by using up to 12 cores, and do not observe any degradation when using up to 24 cores. Furthermore, the profiling results of our implementation show that even at peak throughput contention between threads is minimal, suggesting that the throughput would continue scaling given a faster network.
Bottom-Up Construction and 2: 1 Balance Refinement of Linear Octrees in Parallel

In this article, we propose new parallel algorithms for the construction and 2:1 balance refinement of large linear octrees on distributed memory machines. Such octrees are used in many problems in computational science and engineering, e.g., object representation, image analysis, unstructured meshing, finite elements, adaptive mesh refinement, and N-body simulations. Fixed-size scalability and isogranular analysis of the algorithms using an MPI-based parallel implementation was performed on a variety of input data and demonstrated good scalability for different processor counts (1 to 1024 processors) on the Pittsburgh Supercomputing Center's TCS-1 AlphaServer. The results are consistent for different data distributions. Octrees with over a billion octants were constructed and balanced in less than a minute on 1024 processors. Like other existing algorithms for constructing and balancing octrees, our algorithms have $\mathcal{O}(N\log N)$ work and $\mathcal{O}(N)$ storage complexity. Under reasonable assumptions on the distribution of octants and the work per octant, the parallel time complexity is $\mathcal{O}(\frac{N}{n_p}\log(\frac{N}{n_p})+n_p\log n_p)$, where $N$ is the size of the final linear octree and $n_p$ is the number of processors.
Bioavailability of Dietary Polyphenols and Gut Microbiota Metabolism: Antimicrobial Properties

Polyphenolic compounds are plant nutraceuticals showing a huge structural diversity, including chlorogenic acids, hydrolyzable tannins, and flavonoids (flavonols, flavanones, flavan-3-ols, anthocyanidins, isoflavones, and flavones). Most of them occur as glycosylated derivatives in plants and foods. In order to become bioactive at human body, these polyphenols must undergo diverse intestinal transformations, due to the action of digestive enzymes, but also by the action of microbiota metabolism. After elimination of sugar tailoring (generating the corresponding aglycons) and diverse hydroxyl moieties, as well as further backbone reorganizations, the final absorbed compounds enter the portal vein circulation towards liver (where other enzymatic transformations take place) and from there to other organs, including behind the digestive tract or via blood towards urine excretion. During this transit along diverse tissues and organs, they are able to carry out strong antiviral, antibacterial, and antiparasitic activities. This paper revises and discusses these antimicrobial activities of dietary polyphenols and their relevance for human health, shedding light on the importance of polyphenols structure recognition by specific enzymes produced by intestinal microbial taxa.
Influence of autonomic nervous dysfunction characterizing effect of diabetes mellitus on heart rate response and exercise capacity in patients undergoing cardiac rehabilitation for acute myocardial infarction.

BACKGROUND The aim of this study was to clarify the influence of sympathetic and parasympathetic nerve (SN and PN) dysfunction on the heart rate (HR) response to exercise and the exercise capacity of patients with acute myocardial infarction (AMI) and diabetes mellitus (DM). METHODS AND RESULTS Fifty-two male patients who underwent cardiopulmonary exercise testing (CPX) 1 month after onset of AMI were divided into 2 groups: (DM (+) group, n=20; DM (-) group, n=32). HR, peak oxygen uptake (VO2peak), and plasma norepinephrine (NE) levels were measured during CPX. The high-frequency power (HF) was analyzed by HR variability. The DeltaHR/logDeltaNE obtained from changes of HR and NE from rest to peak exercise and HR change from baseline to the minimum HF (DeltaHRHF) were calculated as parameters of HR response derived from SN and PN activities, respectively. DeltaHR, VO2peak, DeltaHR/logDeltaNE, and DeltaHRHF were significantly lower in the DM (+) group than in the DM (-) group, and both of them showed positive correlations with VO2peak. CONCLUSION An inadequate HR response to exercise is a major factor causing a decline of exercise capacity, which is derived from both of SN and PN dysfunction, in AMI patients with DM.
Distinct effects of contrast and color on subjective rating of fearfulness

Natural scenes provide important affective cues for observers to avoid danger. From an adaptationist perspective, such cues affect the behavior of the observer and shape the evolution of the observer’s response. It is evolutionarily significant for individuals to extract affective information from the environment as quickly and as efficiently as possible. However, the nearly endless variations in physical appearance of natural scenes present a fundamental challenge for perceiving significant visual information. How image-level properties, such as contrast and color, influence the extraction of affective information leading to subjective emotional perception is unclear. On the one hand, studies have shown that visual perception and emotional perception seem to interact with each other at the earliest stages in cortical processing. On the other hand, it is important for high-level subjective ratings to be invariant to low-level visual properties. Using a psychophysical approach and signal detection theory (SDT), we tested how contrast and color influenced fearfulness ratings of a set of natural scene pictures that varied in contents and in levels of fearfulness. Image contrast influenced perceptual sensitivity but not the decision criterion of fearfulness rating, whereas color affected the decision criterion but not perceptual sensitivity. These results show that different low-level visual features contribute independently to sensitivity or decision criterion in affective perception, suggesting distinct interactions between visual cognition and affective processing. Specifically, our naturalistic approach using a novel stimulus set, combined with SDT, has demonstrated two dissociable types of cognitive mechanisms underlying how image-level properties leverage the extraction of affective information in natural vision.
Circulating CD34+ Progenitor Cells and Risk of Mortality in a Population With Coronary Artery Disease

Rationale: Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. Objectives: To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. Methods and Results: Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34+ and CD34+/CD133+ cell counts and risk of death in cohort 1 (&bgr;=−0.92, P=0.043 and &bgr;=−1.64, P=0.019, respectively) that was confirmed in cohort 2 (&bgr;=−1.25, P=0.020 and &bgr;=−1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67–7.50) and 2.46 (1.18–5.13), respectively. CD34+/CD133+ cell counts improved risk prediction metrics beyond standard risk factors. Conclusions: Reduced circulating progenitor cell counts, identified primarily as CD34+ mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.
Splatting lines: an efficient method for illustrating 3D surfaces and volumes

While 3D line drawing techniques have become well established in the past decade, most are only suitable for polygonal meshes. This paper presents splatting lines, a unified framework for generating line drawings from various types of 3D models, including point clouds, volumes, and polygonal meshes. In contrast to the existing mesh-based approaches, our method takes a densely sampled point cloud as input. It renders two diffuse shading images using splatting with different parameters and then generates line drawings by subtracting these images. Our point-based approach can be easily extended to polygonal meshes and volumes by an efficient (iso-)surface sampling method. Our method is highly efficient and it does not require any pre-computation. It is also more robust to the mesh tessellation than existing mesh-based techniques. Experimental results indicate the advantages of our method in terms of both performance and quality.