Miracle-dz/UniFAR-FTUs huggingface dataset:
Bayesian evolutionary model testing in the phylogenomics era: matching model complexity with computational efficiency

MOTIVATION The advent of new sequencing technologies has led to increasing amounts of data being available to perform phylogenetic analyses, with genomic data giving rise to the field of phylogenomics. High-performance computing is becoming an indispensable research tool to fit complex evolutionary models, which take into account specific genomic properties, to large datasets. Here, we perform an extensive Bayesian phylogenetic model selection study, comparing codon and nucleotide substitution models, including codon position partitioning for nucleotide data as well gene-specific substitution models for both data types. For the best fitting partitioned models, we also compare independent partitioning with standard diffuse prior specification to conditional partitioning via hierarchical prior specification. To compare the different models, we use state-of-the-art marginal likelihood estimation techniques, including path sampling and stepping-stone sampling. RESULTS We show that a full codon model best describes the features of a whole mitochondrial genome dataset, consisting of 12 protein-coding genes, but only when each gene is allowed to evolve under a separate codon model. However, when using hierarchical prior specification for the partition-specific parameters instead of independent diffuse priors, codon position partitioned nucleotide models can still outperform standard codon models. We demonstrate the feasibility of fitting such a combination of complex models using the BEAGLE library for BEAST in combination with recent graphics cards. We argue that development and use of such models needs to be accompanied by state-of-the-art marginal likelihood estimators because the more traditional and computationally less demanding estimators do not offer adequate accuracy.
Embryo Adoption: Some Further Considerations

Recent discussions of embryo adoption have sought to make sense of the teaching of the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae which appeared to provide a negative judgment on such a practice. This article aims to provide a personalist account of the process of fertilization and implantation that might serve as the basis for the negative judgment of the CDF document. In doing so, it relies upon the idea that a person, including an embryo, is not to be considered in isolation, but always in relation to God and to others. This approach extends the substantialist conceptualizations commonly employed in discussions of this issue. More generally, the article seeks to highlight the value of a personalist re-framing for an understanding of the moral questions surrounding the beginning of life. Lay summary: This article seeks to make sense of what appears to be a clear-cut rejection, set out in the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae, of the proposal for women to “adopt” surplus frozen embryos. It draws upon more recently developed modes of philosophical/theological reasoning to argue that, in human procreation, both fertilization and implantation represent constitutive dimensions of divine creative activity and so must be protected from manipulative technological intervention. Since embryo adoption requires this kind of technology, it makes sense for the Church document not to approve it.
Probing the Dynamics of Identified Neurons with a Data-Driven Modeling Approach

In controlling animal behavior the nervous system has to perform within the operational limits set by the requirements of each specific behavior. The implications for the corresponding range of suitable network, single neuron, and ion channel properties have remained elusive. In this article we approach the question of how well-constrained properties of neuronal systems may be on the neuronal level. We used large data sets of the activity of isolated invertebrate identified cells and built an accurate conductance-based model for this cell type using customized automated parameter estimation techniques. By direct inspection of the data we found that the variability of the neurons is larger when they are isolated from the circuit than when in the intact system. Furthermore, the responses of the neurons to perturbations appear to be more consistent than their autonomous behavior under stationary conditions. In the developed model, the constraints on different parameters that enforce appropriate model dynamics vary widely from some very tightly controlled parameters to others that are almost arbitrary. The model also allows predictions for the effect of blocking selected ionic currents and to prove that the origin of irregular dynamics in the neuron model is proper chaoticity and that this chaoticity is typical in an appropriate sense. Our results indicate that data driven models are useful tools for the in-depth analysis of neuronal dynamics. The better consistency of responses to perturbations, in the real neurons as well as in the model, suggests a paradigm shift away from measuring autonomous dynamics alone towards protocols of controlled perturbations. Our predictions for the impact of channel blockers on the neuronal dynamics and the proof of chaoticity underscore the wide scope of our approach.
Molecular analysis of SSN6, a gene functionally related to the SNF1 protein kinase of Saccharomyces cerevisiae

Mutations in the SSN6 gene suppress the invertase derepression defect caused by a lesion in the SNF1 protein kinase gene. We cloned the SSN6 gene of Saccharomyces cerevisiae and identified its 3.3-kilobase poly(A)-containing RNA. Disruption of the gene caused phenotypes similar to, but more severe than, those caused by missense mutations: high-level constitutivity for invertase, clumpiness, temperature-sensitive growth, alpha-specific mating defects, and failure to homozygous diploids to sporulate. In contrast, the presence of multiple copies of SSN6 interfered with derepression of invertase. An ssn6 mutation was also shown to cause glucose-insensitive expression of a GAL10-lacZ fusion and maltase. The mating defects of MAT alpha ssn6 strains were associated with production of two a-specific products, a-factor and barrier, and reduced levels of alpha-factor; no deficiency of MAT alpha 2 RNA was detected. We showed that ssn6 partially restored invertase expression in a cyr1-2 mutant, although ssn6 was clearly not epistatic to cyr1-2. We also determined the nucleotide sequence of SSN6, which is predicted to encode a 107-kilodalton protein with stretches of polyglutamine and poly(glutamine-alanine). Possible functions of the SSN6 product are discussed.
Globalization, Development, and International Institutions: Normative and Positive Perspectives

At the conclusion of World War II, several international institutions were created to manage the world economy and prevent another Great Depression. These institutions include the International Monetary Fund (IMF), the International Bank for Reconstruction and Development (now called the World Bank), and the General Agreement on Tariffs and Trade (GATT), which was expanded and institutionalized into the World Trade Organization (WTO) in 1995. These institutions have not only persisted for over five decades, but they have also expanded their mandates, changed their missions, and increased their membership. They have, however, become highly contested. As Stiglitz notes, “International bureaucrats—the faceless symbols of the world economic order—are under attack everywhere…. Virtually every major meeting of the International Monetary Fund, the World Bank and the World Trade Organization is now the scene of conflict and turmoil. ”Helen V. Milner is the B. C. Forbes Professor of Politics and International Affairs at Princeton University and the director of the Center for Globalization and Governance at Princeton's Woodrow Wilson School (hmilner@Princeton.edu). She has written extensively on issues related to international trade, the connections between domestic politics and foreign policy, globalization and regionalism, and the relationship between democracy and trade policy. Her writings include Interests, Institutions, and Information: Domestic Politics and International Relations (1997), Internationalization and Domestic Politics (co-edited with Robert O. Keohane, 1996), “Why the Move to Free Trade? Democracy and Trade Policy in the Developing Countries” (International Organization 2005), “The Optimal Design of International Trade Institutions: Uncertainty and Escape” (coauthored with B. Peter Rosendorff, International Organization, 2001). The author thanks David Baldwin, Chuck Beitz, Robert O. Keohane, Erica Gould, Steve Macedo, Lisa Martin, Thomas Pogge, Tom Romer, and Jim Vreeland for invaluable comments. She also received much useful advice from seminars at Princeton University and the Rockefeller Foundation's Bellagio Study and Conference Center.
Bortezomib in kidney transplantation

Purpose of reviewThe purpose of this review is to evaluate the effectiveness of bortezomib in the recent literature for the prevention and treatment of kidney transplant rejection. Recent findingsSeveral studies have analyzed bortezomib alone and in comparison to more traditional immunosuppressive agents during the last 2 years. If administered prior to transplant or soon thereafter, bortezomib appears to lower donor-specific antibody levels and improves graft survival. Its role as a treatment option for antibody-mediated rejection after transplant remains unclear, with limited evidence supporting its long-term success. SummaryBortezomib appears to be a promising early desensitizing agent in the world of kidney transplantation and high short-term success rates have been observed. However, additional randomized trials would be useful to more conclusively demonstrate its effectiveness and optimal administration time in relation to transplant surgery.
When Pinocchio's nose does not grow: belief regarding lie-detectability modulates production of deception

Does the brain activity underlying the production of deception differ depending on whether or not one believes their deception can be detected? To address this question, we had participants commit a mock theft in a laboratory setting, and then interrogated them while they underwent functional MRI (fMRI) scanning. Crucially, during some parts of the interrogation participants believed a lie-detector was activated, whereas in other parts they were told it was switched-off. We were thus able to examine the neural activity associated with the contrast between producing true vs. false claims, as well as the independent contrast between believing that deception could and could not be detected. We found increased activation in the right amygdala and inferior frontal gyrus (IFG), as well as the left posterior cingulate cortex (PCC), during the production of false (compared to true) claims. Importantly, there was a significant interaction between the effects of deception and belief in the left temporal pole and right hippocampus/parahippocampal gyrus, where activity increased during the production of deception when participants believed their false claims could be detected, but not when they believed the lie-detector was switched-off. As these regions are associated with binding socially complex perceptual input and memory retrieval, we conclude that producing deceptive behavior in a context in which one believes this deception can be detected is associated with a cognitively taxing effort to reconcile contradictions between one's actions and recollections.
Cannabinoid Receptor Type 1 Located on Presynaptic Terminals of Principal Neurons in the Forebrain Controls Glutamatergic Synaptic Transmission

It is widely accepted that cannabinoids regulate GABA release by activation of cannabinoid receptor type 1 (CB1). Results obtained from a variety of brain regions consistently indicate that cannabinoid agonists can also reduce glutamatergic synaptic transmission. However, there are still conflicting data concerning the role of CB1 in cannabinoid-induced inhibition of glutamatergic transmission in cortical areas. Here, we provide direct evidence that activation of CB1 on terminals of principal neurons controls excitatory synaptic responses in the forebrain. In slices of the basolateral amygdala, the CA1 region of the hippocampus, and the primary somatosensory cortex of wild-type mice, application of the CB1 agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55,212-2; WIN) (5 μm) reduced evoked excitatory postsynaptic responses. In contrast, in slices obtained from conditional mouse mutants lacking CB1 in all principal forebrain neurons but not in GABAergic interneurons (CB1f/f;CaMKIIαCre), WIN no longer affected glutamatergic synaptic transmission in any of the brain regions tested. Compatible with a presynaptic mechanism, WIN did not change the sensitivity to focally uncaged l-glutamate. WIN reduced glutamatergic responses in slices obtained from mice lacking CB1 exclusively in GABAergic neurons (CB1f/f;Dlx5/6-Cre), thus excluding the involvement of CB1 expressed on GABAergic neurons in this effect of the drug. The present data strongly indicate that excitatory synaptic transmission in forebrain areas is directly modulated by CB1 expressed on presynaptic axon terminals originating from glutamatergic neurons.
Advanced unsupervised joint prosody labeling and modeling for Mandarin speech and its application to prosody generation for TTS

Motivated by the success of the unsupervised joint prosody labeling and modeling (UJPLM) method for Mandarin speech on modeling of syllable pitch contour in our previous study, in this paper, the advanced UJPLM (A-UJPLM) method is proposed based on UJPLM to jointly label prosodic tags and model syllable pitch contour, duration and energy level. Experimental results on the Sinica Treebank corpus showed that most prosodic tags labeled were linguistically meaningful and the model parameters estimated were interpretable and generally agreed with other previous study. In virtue of the functions given by the model parameters, an application of A-UJPLM to the prosody generation for Mandarin TTS is proposed. Experimental results showed that the proposed method performed well. Most predicted prosodic features matched well to their original counterparts. This also reconfirmed the effectiveness of the A-UJPLM method.
Fetal Ventriculomegaly: Investigating Additional Brain Abnormalities by using MR Imaging

Background and Purpose: Fetal ventriculomegaly (VM), is known to have a prevalence of association with other brain abnormalities. By using in utero MR imaging (iuMR), we aimed to determine the prevalence of brain abnormalities other than VM and investigate the hypothesis that the prevalence of having additional brain abnormalities (ABA) increases with the degree of VM. Materials and Methods: We reviewed iuMR images of 75 fetuses. The enlarged ventricles were graded as mild (≤ 12mm), moderate (> 12 to ≤15mm), and severe (> 15mm). Prevalence of having ABA were calculated and compared among groups with different grades of VM. Results: ABA was shown in 67% of fetuses. The most frequent ABA was agenesis of the corpus callosum. The prevalence of having ABA increased with the degree of fetal VM in all groups. Severe VM was associated with a higher prevalence of ABA when compared with mild VM in the prevalence of having ABA being present when compared with mild VM. Conclusions: The prevalence of having ABA increases with the degree of fetal VM. Caution should be exercised that this trend of ABA does not apply to those fetuses with isolated VM by sonography due to the different subjects studied.
Nationwide Survey Shows that Methicillin-ResistantStaphylococcus aureus Strains Heterogeneously and Intermediately Resistant to Vancomycin Are Not Disseminated throughout Japanese Hospitals

ABSTRACT A total of 6,625 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates obtained from 278 hospitals throughout Japan were obtained between November and December 1997 and were examined for their sensitivities to vancomycin using Mueller Hinton (MH), brain heart infusion (BHI), agar plates, or the broth microdilution method. A concentrated inoculum of an MRSA strain or the use of highly enriched medium, such as BHI medium, allows an individual cell to grow on agar plates containing a vancomycin concentration greater than the MIC for the parent strain. However, cells of the colonies which grew on BHI agar plates containing the higher vancomycin concentrations did not acquire a level of vancomycin resistance greater than that of the parent strain and were not subpopulations of heterogeneously vancomycin-resistant MRSA. There was no significance in the fact that these colonies grew on the higher concentration of vancomycin: none showed stable resistance to vancomycin at a concentration above the MIC for the parent strain, and no cell from these colonies showed a relationship between the MIC and the ability of these colonies to grow on higher concentrations of vancomycin. The vancomycin MIC was not above 2 μg/ml for any of the cells originating from these colonies. No Mu3-type heterogeneously resistant MRSA strains, which constitutively produce subpopulations from MRSA clinical isolates with intermediate vancomycin resistance at a high frequency, were detected. There was a unipolar distribution of the MICs ranging from 0.25 to 2 μg of vancomycin/ml among the 6,625 MRSA clinical isolates, indicating that there was no Mu50-type intermediately vancomycin-resistant MRSA (MIC, 8 μg/ml by National Committee for Clinical Laboratory Standards criteria) among the clinical isolates, and there was no evidence of dissemination of Mu3-type MRSA heteroresistant to vancomycin.
Neuroprotective Effects Of Curcumin

Turmeric, derived from the plant Curcuma longa, is a gold-colored Spice that has been used as a traditional medicine. Curcumin (CUR), the principal curcuminoid of turmeric, which gives the yellow color to turmeric, is now recognized as being responsible for most of the therapeutic effects. It has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial and antifungal as well as anticancer activities. The loss of functional neurons and synapses lead to neurodegenerative diseases. Current treatments for most of these diseases had not succeeded adequate until now. Both of oxidative damage and inflammation have been proved as having roles in age-related neurodegenerative diseases. Antioxidants have been demonstrated to protect neurons against a variety of experimental neurodegenerative conditions. A number of experimental studies indicate that CUR, as an antioxidant protects the brain against various oxidative stressors. CUR is a powerful scavenger of superoxide anions, and it has both neuroprotective and anti-aging effects. CUR can cross the blood-brain barrier (BBB) and reach the brain. Accumulating cell culture and animal model data show that dietary CUR is a strong candidate for use in the prevention or treatment of Neurodegenerative diseases includes Alzheimer's disease, Parkinson's disease and multiple sclerosis. Also CUR showed protection against Ischemic cerebral stroke, epilepsy and depression.
Improving symptoms of pain, erectile dysfunction, and depression in patients on dialysis.

As nephrologists, we spend hours on monthly dialysis rounds examining and fine-tuning numbers: hemoglobin, iron saturation, ferritin, phosphorus, calcium, albumin, intact parathyroid hormone, and Kt/V, among others. Yet our dialysis patients are less concerned about whether they meet Kidney Disease
Stochastic-Resonance Based Iterative Detection for Serially-Concatenated Turbo Codes

In this letter, the concept of multiple serially-concatenated codes is invoked in the context of stochastic resonance (SR), where the achievable performance is improved by increasing noise power. More specifically, the receiver's iterative decoding process is characterized with the aid of extrinsic information transfer (EXIT) charts, such that the SR effect induced by a non-linear component is taken into account. Our simulation results demonstrate that although the SR demodulator's log-likelihood ratio (LLR) outputs are not Gaussian distributed, the corresponding EXIT trajectory matches the prediction from the associated inner- and outer-codes' EXIT curves, while reaching the perfect convergence point in terms of mutual information. Therefore, an infinitesimally low bit-error ratio (BER) is attained by appropriately designing the channel code's parameters based on EXIT charts.
Time‐Varying Storage–Water Age Relationships in a Catchment With a Mediterranean Climate

Recent studies on the relationships between catchment storage and water ages using Travel Time Distributions (TTDs), Residence Time Distributions (RTDs), and StorAge Selection (SAS) functions have led to the hypothesis that streamflow preferentially mobilizes younger water when catchment storage is high. This so‐called “Inverse Storage Effect” (ISE) needs further evaluation in more catchments with diverse climates and physiographical features. In this work, we assessed the validity of the ISE in WS10 (H. J. Andrews forest, Oregon, USA), a forested headwater catchment in a Mediterranean climate. A conceptual model of the catchment, developed based on experimental observations of water flow paths in WS10, was calibrated to streamflow and δ18O in streamflow. Based on the calibrated model results, we determined RTDs, and streamflow TTDs and SAS functions by assuming that the soil reservoir and the groundwater reservoir act as well‐mixed systems. The streamflow SAS functions and travel time dynamics showed that the ISE generally applies in WS10. Yet, during transitions from dry summer periods to wet winter periods and vice versa, the marked seasonal climate caused rapid and strong storage variations in the catchment, which led to deviations from the ISE. The seasonality of streamflow travel times in WS10 is the result of the seasonal contributions of younger water from the hillslopes added to the rather constant groundwater contributions of older water. The streamflow SAS functions were able to capture the relative importance of contrasting flow paths in the soils and in the bedrock highlighted by previous studies in WS10.
Diversity in a hidden world: potential and limitation of next‐generation sequencing for surveys of molecular diversity of eukaryotic microorganisms

With the delivery of millions of sequence reads in a single experiment, next‐generation sequencing (NGS) is currently revolutionizing surveys of microorganism diversity. In particular, when applied to Eukaryotes, we are still lacking a rigorous comparison of morphological and NGS‐based diversity estimates. In this report, we studied the diversity and the seasonal community turnover of alveolates (Ciliophora and Dinophyceae) in an oligotrophic freshwater lake by SSU amplicon sequencing with NGS as well as by classical morphological analysis. We complemented the morphological analysis by single‐cell PCR followed by Sanger sequencing to provide an unambiguous link to the NGS data. We show that NGS and morphological analyses generally capture frequency shifts of abundant taxa over our seasonal samples. The observed incongruencies are probably largely due to rDNA copy number variation among taxa and heterogeneity in the efficiency of cell lysis. Overall, NGS‐based amplicon sequencing was superior in detecting rare species. We propose that in the absence of other nuclear markers less susceptible to copy number variation, rDNA‐based diversity studies need to be adjusted for confounding effects of copy number variation.