Miracle-dz/UniFAR-FTUs huggingface dataset:
High density continuous production of murine pluripotent cells in an acoustic perfused bioreactor at different oxygen concentrations.

Strategies for the production of pluripotent stem cells (PSCs) rely on serially dissociated adherent or aggregate-based culture, consequently limiting robust scale-up of cell production, on-line control and optimization of culture conditions. We recently developed a method that enables continuous (non-serially dissociated) suspension culture-mediated reprogramming to pluripotency. Herein, we use this method to demonstrate the scalable production of PSCs and early derivatives using acoustic filter technology to enable continuous oxygen-controlled perfusion culture. Cell densities of greater than 1 × 10⁷ cells/mL were achieved after 7 days of expansion at a specific growth rate (µ) of 0.61 ± 0.1 day⁻¹ with a perfusion rate (D) of 5.0 day⁻¹. A twofold increase in maximum cell density (to greater than 2.5 × 10⁷ cells/mL) was achieved when the medium dissolved oxygen was reduced (5% DO). Cell densities and viabilities >80% were maintained for extended production periods during which maintenance of pluripotency was confirmed by stable expression of pluripotency factors (SSEA-1 and Nanog), as well as the capacity to differentiate into all three germ layers. This work establishes a versatile biotechnological platform for the production of pluripotent cells and derivatives in an integrated, scalable and intensified stirred suspension culture.
Map retrieval in 3D using view-dependent local map descriptor

Map retrieval, the problem of similarity search over a large collection of 3D pointset maps previously built by mobile robots, is crucial for autonomous navigation in indoor and outdoor environments. Bag-of-words (BoW) methods constitute a popular approach to map retrieval; however, these methods have extremely limited descriptive ability because they ignore the spatial layout information of the local features. The main contribution of this paper is an extension of the bag-of-words map retrieval method to enable the use of spatial information from local features. Our strategy is to explicitly model a unique viewpoint of an input local map; the pose of the local feature is defined with respect to this unique viewpoint, and can be viewed as an additional invariant feature for discriminative map retrieval. Specifically, we wish to determine a unique viewpoint that is invariant to moving objects, clutter, occlusions, and actual viewpoints. Hence, we perform scene parsing to analyze the scene structure, and consider the "center" of the scene structure to be the unique viewpoint. Our scene parsing is based on a Manhattan world assumption that imposes a quasi-Manhattan world constraint to enable the robust detection of a scene structure that is invariant to clutter and moving objects. Experimental results using the publicly available University of Michigan North Campus Long-Term Vision and LIDAR Dataset (NCLT dataset [1]) validate the efficacy of the proposed approach.
The Skull of Phyllomedusa sauvagii (Anura, Hylidae)

The hylid genus Phyllomedusa comprises charismatic frogs commonly known as monkey, leaf or green frogs, and is the most diverse genus of the subfamily Phyllomedusinae, including about 31 species. Although there is some information about the anatomy of these frogs, little is known about the osteology. Here the adult skull of Phyllomedusa sauvagii, both articulated and disarticulated, is described and the intraspecific variation is reported. Additionally, cartilage associated with the adult skull, such as the nasal capsules, auditory apparatus, and hyobranchial apparatus, are included in the analysis. Further examination of disarticulated bones reveals their remarkable complexity, specifically in the sphenethmoid and of the oocipital region. The description of disarticulated bones is useful for the identification of fossil remains as well as providing morphological characteristics that are phylogenetically informative. When comparing the skull morphology with the available information of other species of the genus, Phyllomesusa sauvagii skull resembles more that of P. vaillantii and P. venusta than P. atelopoides. Anat Rec, 299:557–572, 2016. © 2016 Wiley Periodicals, Inc.
PCR Primers That Amplify Fungal rRNA Genes from Environmental Samples

ABSTRACT Two PCR primer pairs were designed to amplify rRNA genes (rDNA) from all four major phyla of fungi: Ascomycota,Basidiomycota, Chytridomycota, andZygomycota. PCRs performed with these primers showed that both pairs amplify DNA from organisms representing the major taxonomic groups of fungi but not from nonfungal sources. To test the ability of the primers to amplify fungal rDNA from environment samples, clone libraries from two avocado grove soils were constructed and analyzed. These soils possess different abilities to inhibit avocado root rot caused by Phythophthora cinnamomi. Analysis of the two rDNA clone libraries revealed differences in the two fungal communities. It also revealed a markedly different depiction of the soil fungal community than that generated by a culture-based analysis, confirming the value of rDNA-based approaches for identifying organisms that may not readily grow on agar media. Additional evidence of the usefulness of the primers was obtained by identifying fungi associated with avocado leaves. In both the soil and leaf analyses, no nonfungal rDNA sequences were identified, illustrating the selectivity of these PCR primers. This work demonstrates the ability of two newly developed PCR primer sets to amplify fungal rDNA from soil and plant tissue, thereby providing unique tools to examine this vast and mostly undescribed community of organisms.
Red Clover HCT2, a Hydroxycinnamoyl-Coenzyme A:Malate Hydroxycinnamoyl Transferase, Plays a Crucial Role in Biosynthesis of Phaselic Acid and Other Hydroxycinnamoyl-Malate Esters in Vivo1[OA]

In red clover (Trifolium pratense) leaves, phaselic acid (2-O-caffeoyl-l-malate) accumulates to several mmol kg−1 fresh weight and is a crucial component of a natural system that prevents protein breakdown during harvest and storage of this forage crop. Previously, we identified HCT2, a red clover gene encoding a hydroxycinnamoyl-Coenzyme A (CoA) hydroxycinnamoyl transferase capable of transferring p-coumaroyl and caffeoyl moieties from their CoA derivatives to malic acid to form the corresponding hydroxycinnamoyl-malate esters in vitro. Here, we carried out a detailed kinetic analysis of the enzyme and examined its in vivo function in red clover via reverse genetics. The kinetic analysis indicates that in vitro, despite similar Km values for the tested hydroxycinnamoyl-CoA derivatives, HCT2 favors transfer to malate of p-coumaroyl and feruloyl moieties over caffeoyl moieties by greater than 5-fold. Reverse reaction (transfer of hydroxycinnamoyl moieties from malate to CoA) by HCT2 was observed with p-coumaroyl-malate but not phaselic acid. Analysis of red clover plants down-regulated for HCT2 expression via RNA interference showed a significant and substantial correlation between HCT2 mRNA levels and phaselic acid accumulation (P < 0.005). In several of the HCT2-silenced plants, phaselic acid and p-coumaroyl-malate levels were reduced to <5% that of wild-type controls. These reductions resulted in easily observable phenotypes including reduced polyphenol oxidase-mediated browning and a reduction in blue epidermal fluorescence under ultraviolet light. These results demonstrate a crucial role for HCT2 in phaselic acid accumulation in red clover and define a previously undescribed pathway for the biosynthesis of hydroxycinnamoyl-malate esters in plants.
Changing Psychiatric Perception of African-Americans With Affective Disorders

Abstract This article explored the origins and implications of the underdiagnosis of affective disorders in African-Americans. MEDLINE and old collections were searched using relevant key words. Reference lists from the articles that were gathered from this procedure were reviewed. The historical record indicated that the psychiatric perception of African-Americans with affective disorders changed significantly during the last 200 years. In the antebellum period, the mental disorders of slaves mostly went unnoticed. By the early 20th century, African-Americans were reported to have high rates of manic-depressive disorder compared with whites. By the mid-century, rates of manic-depressive disorder in African-Americans plummeted, whereas depression remained virtually nonexistent. In recent decades, diagnosed depression and bipolar disorder, whether in clinical or research settings, were inexplicably low in African-Americans compared with whites. Given these findings, American psychiatry needs to appraise the deep-seated effects of historical stereotypes on the diagnosis and treatment of African-Americans.
Up in the Tree – The Overlooked Richness of Bryophytes and Lichens in Tree Crowns

Assessing diversity is among the major tasks in ecology and conservation science. In ecological and conservation studies, epiphytic cryptogams are usually sampled up to accessible heights in forests. Thus, their diversity, especially of canopy specialists, likely is underestimated. If the proportion of those species differs among forest types, plot-based diversity assessments are biased and may result in misleading conservation recommendations. We sampled bryophytes and lichens in 30 forest plots of 20 m × 20 m in three German regions, considering all substrates, and including epiphytic litter fall. First, the sampling of epiphytic species was restricted to the lower 2 m of trees and shrubs. Then, on one representative tree per plot, we additionally recorded epiphytic species in the crown, using tree climbing techniques. Per tree, on average 54% of lichen and 20% of bryophyte species were overlooked if the crown was not been included. After sampling all substrates per plot, including the bark of all shrubs and trees, still 38% of the lichen and 4% of the bryophyte species were overlooked if the tree crown of the sampled tree was not included. The number of overlooked lichen species varied strongly among regions. Furthermore, the number of overlooked bryophyte and lichen species per plot was higher in European beech than in coniferous stands and increased with increasing diameter at breast height of the sampled tree. Thus, our results indicate a bias of comparative studies which might have led to misleading conservation recommendations of plot-based diversity assessments.
Sensitivity Analysis, Dominant Factors, and Robustness of the ECETOC TRA v3, Stoffenmanager 4.5, and ART 1.5 Occupational Exposure Models

Occupational exposure modeling is widely used in the context of the E.U. regulation on the registration, evaluation, authorization, and restriction of chemicals (REACH). First tier tools, such as European Centre for Ecotoxicology and TOxicology of Chemicals (ECETOC) targeted risk assessment (TRA) or Stoffenmanager, are used to screen a wide range of substances. Those of concern are investigated further using second tier tools, e.g., Advanced REACH Tool (ART). Local sensitivity analysis (SA) methods are used here to determine dominant factors for three models commonly used within the REACH framework: ECETOC TRA v3, Stoffenmanager 4.5, and ART 1.5. Based on the results of the SA, the robustness of the models is assessed.
Event-Related Potentials Elicited By Face Identity Processing In Elderly Adults With Cognitive Impairment

Background/Study Context: Patients with mild Alzheimer's disease and mild cognitive impairment show selective loss of knowledge regarding facial identification. Methods: The authors focus on decline effects on event-related potentials (ERPs) P100, N170, N250, and N400, associated with the processing of facial identity. Different famous and unknown faces were presented in explicit and implicit familiarity tasks. Results: Patients with cognitive impairment showed modulations on P100 and N170 and greater activity in prefrontal areas in the earlier component. In healthy elderly individuals, but not in patients, famous faces modulated the long-latency ERPs N250 and N400, related to the access and retrieval of stored facial-related information, respectively. Conclusion: ERPs have potential as markers of neurodegenerative disease such as dementia. The neural systems supporting facial identification may differ in normal and cognitively impaired older adults.
Statistical mechanics of error exponents for error-correcting codes

Error exponents characterize the exponential decay, when increasing message length, of the probability of error of many error-correcting codes. To tackle the long-standing problem of computing them exactly, we introduce a general, thermodynamic, formalism that we illustrate with maximum-likelihood decoding of low-density parity-check codes on the binary erasure channel and the binary symmetric channel. In this formalism, we apply the cavity method for large deviations to derive expressions for both the average and typical error exponents, which differ by the procedure used to select the codes from specified ensembles. When decreasing the noise intensity, we find that two phase transitions take place, at two different levels: a glass to ferromagnetic transition in the space of codewords and a paramagnetic to glass transition in the space of codes.
Respiratory symptoms questionnaire for asthma epidemiology: validity and reproducibility.

BACKGROUND: There is a need for a new respiratory symptoms questionnaire for use in epidemiological research in asthma. METHOD: A questionnaire was designed following a pilot study in 78 subjects. It contains nine questions on symptoms such as wheeze and difficulty with breathing in defined circumstances such as exercise and sleep. It was completed by 211 adults and validated by comparison with a self reported history of asthma and with bronchial hyperresponsiveness to histamine. Its short term reproducibility was measured by three repeat administrations over two weeks. RESULTS: Subjects with asthma (n = 33), particularly those having had an asthma attack in the last year (n = 23), were more likely to report any symptom and to report a greater number of symptoms than those without asthma. The same relationship was found for bronchial hyperresponsiveness and symptoms. Either two or more, or three or more, symptoms appeared to be good indices of self reported asthma and bronchial hyperresponsiveness, or both, with a high sensitivity (65-91%) and specificity (85-96%). Reproducibility was good, with few subjects changing the number of symptoms reported by more than one symptom and none by more than four symptoms. The results compared favourably with those from questions on phlegm production from the MRC questionnaire and were better than those reported for the MRC wheeze questions. CONCLUSIONS: The questionnaire will be useful for epidemiological research on asthma and could form part of a new standardised questionnaire with wide applications.
Design of Prodrugs to Enhance Colonic Absorption by Increasing Lipophilicity and Blocking Ionization

Prodrugs are chemistry-enabled drug delivery modifications of active molecules designed to enhance their pharmacokinetic, pharmacodynamic and/or biopharmaceutical properties. Ideally, prodrugs are efficiently converted in vivo, through chemical or enzymatic transformations, to the active parent molecule. The goal of this work is to enhance the colonic absorption of a drug molecule with a short half-life via a prodrug approach to deliver sustained plasma exposure and enable once daily (QD) dosing. The compound has poor absorption in the colon and by the addition of a promoiety to block the ionization of the molecule as well as increase lipophilicity, the relative colonic absorption increased from 9% to 40% in the retrograde dog colonic model. A combination of acceptable solubility and stability in the gastrointestinal tract (GI) as well as permeability was used to select suitable prodrugs to optimize colonic absorption.
Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

Background Transcription factors (TF) regulate expression by binding to specific DNA sequences. A binding event is functional when it affects gene expression. Functionality of a binding site is reflected in conservation of the binding sequence during evolution and in over represented binding in gene groups with coherent biological functions. Functionality is governed by several parameters such as the TF-DNA binding strength, distance of the binding site from the transcription start site (TSS), DNA packing, and more. Understanding how these parameters control functionality of different TFs in different biological contexts is a must for identifying functional TF binding sites and for understanding regulation of transcription. Methodology/Principal Findings We introduce a novel method to screen the promoters of a set of genes with shared biological function (obtained from the functional Gene Ontology (GO) classification) against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. More than 8000 human (and 23,000 mouse) genes, were assigned to one of 134 GO sets. Their promoters were searched (from 200 bp downstream to 1000 bp upstream the TSS) for 414 known DNA motifs. We optimized the sequence similarity score threshold, independently for every location window, taking into account nucleotide heterogeneity along the promoters of the target genes. The method, combined with binding sequence and location conservation between human and mouse, identifies with high probability functional binding sites for groups of functionally-related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were tested experimentally. Conclusions/Significance We identified reliably functional TF binding sites. This is an essential step towards constructing regulatory networks. The promoter region proximal to the TSS is of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.
Author Reply

Sir, We read with great interest the letter in response to our systematic review and meta‐analysis assessing the efficacy of bedaquiline versus placebo for management of multidrug‐resistant tuberculosis. [1] As per our interpretation of the letter, authors were surprised by the findings of our systematic review and meta‐analysis and made some suggestions on the approach for meta‐analysis. For example, authors state that a fixed model, instead of random effects model should have been used due to lack of heterogeneity. Unfortunately, the authors are not aware of the latest methods for the conduct of meta‐analysis. As per the Cochrane Handbook of Systematic Reviews, the choice of model should not be determined on the basis of observed heterogeneity but rather following a prespecified protocol. That is, the choice of fixed versus random effect should be decided a priori and not post hoc. Further, in the case of the fixed‐effect model the key assumption is that the true effect size is same in all studies, which simply is implausible. In addition, there is never a case when two trials are exactly the same. That is, the trials may be similar but still have slight differences in terms of setting, patient populations, caregivers, etc., Therefore, when studies from the published literature are used in a meta‐analysis, the random‐effects model is generally considered a more plausible match. [2,3] On another note, the results remain unchanged regardless of the model used.
New treatments for chronic hepatitis C

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.
Real-time visual perception : detection and localisation of static and moving objects from a moving stereo rig

Perception of the surrounding environment is one of the many tasks an automated vehicle has to achieve in complex and ever-changing surroundings. This typically includes several distinct sub-tasks, such as map-building, localisation, static obstacles detection, pedestrian detection,. Some of these tasks are nowadays very well known, such as map-building, whereas the perception, localisation and classification of moving objects from a moving vehicle are in many aspects a work in progress. In this paper, we propose a vision-based approach built on the extensive tracking of numerous visual features over time from a stereo-vision pair. Through on-the-fly environment 3D reconstruction, based on visual clues, we propose an integrated method to detect and localise static and moving obstacles, whose position, orientation and speed vector is estimated. Our implementation runs at the moment in a slow real-time (9fps), and should in the future be enclosed in a more complete, probabilistic pipeline.
Structural prerequisites for endotoxic activity in the Limulus test as compared to cytokine production in mononuclear cells

The structural prerequisites for lipopolysaccharide (LPS) and its partial structures for the activation of the Limulus clotting cascade (Limulus amebocyte lysate [LAL] test) are described and compared with the corresponding requirements for the activation of human immune cells such as mononuclear cells. A necessary, but not sufficient, structural motif for this is the presence of the 4′-phosphate-diglucosamine backbone recognition structure (‘epitope’) in lipid A. High activity is only expressed by assemblies of endotoxins, but this is largely independent of the type of supramolecular aggregate structure. A particular conformation of the epitope within the lipid A assembly must be present, which is influenced by addition of further saccharide units to the lipid A moiety, but also reacts slightly to the acylation pattern. In contrast, the cytokine production of human immune cells induced by LPS sensitively depends on the type of its aggregate structure. In the case of a hexa-acylated bisphosphorylated lipid A structure, high activity is only observed with cubic inverted aggregates. Furthermore, addition of antimicrobial agents (such as polymyxin B) leads to a nearly complete inhibition of cytokine production, whereas the reduction in the Limulus assay is much lower. These data are important since a reliable determination of endotoxin concentrations, in particular with respect to its ability to elicit severe infections, is of high interest.