Miracle-dz/UniFAR-FTUs huggingface dataset:
Allele‐specific gene expression in a wild nonhuman primate population

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype‐phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele‐specific gene expression (ASGE), in the well‐studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis‐regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene–environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis‐regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals.
Deregulated Copper Transport Affects Arabidopsis Development Especially in the Absence of Environmental Cycles1[C][W]

Copper is an essential cofactor for key processes in plants, but it exerts harmful effects when in excess. Previous work has shown that the Arabidopsis (Arabidopsis thaliana) COPT1 high-affinity copper transport protein participates in copper uptake through plant root tips. Here, we show that COPT1 protein localizes to the plasma membrane of Arabidopsis cells and the phenotypic effects of transgenic plants overexpressing either COPT1 or COPT3, the latter being another high-affinity copper transport protein family member. Both transgenic lines exhibit increased endogenous copper levels and are sensitive to the copper in the growth medium. Additional phenotypes include decreased hypocotyl growth in red light and differentially affected flowering times depending on the photoperiod. Furthermore, in the absence of environmental cycles, such as light and temperature, the survival of plants overexpressing COPT1 or COPT3 is compromised. Consistent with altered circadian rhythms, the expression of the nuclear circadian clock genes CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) is substantially reduced in either COPT1- or COPT3-overexpressing plants. Copper affects the amplitude and the phase, but not the period, of the CCA1 and LHY oscillations in wild-type plants. Copper also drives a reduction in the expression of circadian clock output genes. These results reveal that the spatiotemporal control of copper transport is a key aspect of metal homeostasis that is required for Arabidopsis fitness, especially in the absence of environmental cues.
An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases

Malate and lactate dehydrogenases (MDH and LDH) are homologous, core metabolic enzymes that share a fold and catalytic mechanism yet possess strict specificity for their substrates. In the Apicomplexa, convergent evolution of an unusual LDH from MDH produced a difference in specificity exceeding 12 orders of magnitude. The mechanisms responsible for this extraordinary functional shift are currently unknown. Using ancestral protein resurrection, we find that specificity evolved in apicomplexan LDHs by classic neofunctionalization characterized by long-range epistasis, a promiscuous intermediate, and few gain-of-function mutations of large effect. In canonical MDHs and LDHs, a single residue in the active-site loop governs substrate specificity: Arg102 in MDHs and Gln102 in LDHs. During the evolution of the apicomplexan LDH, however, specificity switched via an insertion that shifted the position and identity of this ‘specificity residue’ to Trp107f. Residues far from the active site also determine specificity, as shown by the crystal structures of three ancestral proteins bracketing the key duplication event. This work provides an unprecedented atomic-resolution view of evolutionary trajectories creating a nascent enzymatic function. DOI: http://dx.doi. org/10.7554/eLife.02304. 001
The Cascade-Correlation Neural Network Growing Algorithm using the Matlab Environment

This paper describes the cascade-correlation algorithm as proposed by [2], as well as its implementation in the Matlab environment. The cascade-correlation is presented as a neural network growing technique which allows one to gradually build a network architecture without the need to redefine the number of neurons to be used in a feed forward neural network if it does not converge. Some results are presented for three different experiments that show the capability of the algorithm.
A Survey of Psychological Support Provision for People with Inflammatory Arthritis in Secondary Care in England

Objectives The consequences of inflammatory arthritis can include depression, anxiety and low mood, reducing patients’ quality of life and increasing pressure on the healthcare system. Treatment guidelines recommend psychological support, but data are lacking on the provision available. Methods A postal survey concerning psychological support provision was sent to rheumatology units in 143 acute trusts across England. Nurses from 73 rheumatology units (51%) responded. Results Overall, 73% rated their unit's psychological support provision as ‘inadequate’ and only 4% rated it as ‘good’. Few units believed that psychological support did not fall within their remit (12%), yet only 8% had a psychologist in the team. Most units (68%) did not routinely screen patients to identify psychological difficulties. Referral to other service providers was reported in 42% of units, with 3% very satisfied with this provision. Within units, services containing elements of psychological support ranged from occupational therapy (81%) to psychology/counselling (14%). Psychological approaches used by team members ranged from shared decision making (77%) to cognitive–behavioural approaches (26%). The current barriers to providing psychological support were lack of clinical time and available training (86% and 74%, respectively), and delivery costs (74%). Future facilitators included management support (74%) and availability of skills training (74%). Conclusions Rheumatology units viewed psychological support provision as part of their remit but rated their overall provision as inadequate, despite some team members using psychological skills. To improve provision, clinicians’ training needs must be addressed and organizational support generated, and further research needs to define adequate psychological support provision from the patient perspective. © 2014 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.
Optimal Software Development: A Control Theoretic Approach

We study the problem of optimally allocating effort between software construction and debugging. As construction proceeds, new errors are introduced into the system. The objective is to deliver a system of the highest possible quality (fewest number of errors) subject to the constraint that N system modules are constructed in a specified duration T. If errors are not corrected during construction, then further construction can produce errors at a faster rate. To curb the growth of errors, some of the effort must be taken away from construction and assigned to testing and debugging. A key finding of this model is that the practice of alternating between pure construction and pure debugging is suboptimal. Instead, it is desirable to concurrently construct and debug the system. We extend the above model to integrate decisions traditionally considered "external" such as the time to release the product to the market with those that are typically treated as "internal" such as the division of effort between construction and debugging. Results show that integrating these decisions can yield significant reduction in the overall cost. Also, when competitive forces are strong, it may be better to release a product early (with more errors) than late (with fewer errors). Thus, underestimating the cost of errors in the product may be better than overestimating the cost.
Digits that are not: Generating new types through deep neural nets

For an artificial creative agent, an essential driver of the search for novelty is a value function which is often provided by the system designer or users. We argue that an important barrier for progress in creativity research is the inability of these systems to develop their own notion of value for novelty. We propose a notion of knowledge-driven creativity that circumvent the need for an externally imposed value function, allowing the system to explore based on what it has learned from a set of referential objects. The concept is illustrated by a specific knowledge model provided by a deep generative autoencoder. Using the described system, we train a knowledge model on a set of digit images and we use the same model to build coherent sets of new digits that do not belong to known digit types.
Predicting Innovation Activity in European Manufacturing Firms: A Multi-Country Empirical Study

The purpose of this paper is to investigate the factors that influence the Internal Process Innovation (IPI) Activity of the European manufacturing firms. Moreover, a predictive model is developed that can be used to predict which manufacturing firms are more likely to introduce any new or significantly improve their internal processes. This survey is part of the e-Business Watch, a service launched in 2007 and provided by empirica GmbH to the European Commission, Enterprise and Industry Directorate General, in co-operation with renowned international partners. In the present study, 914 European manufacturing small, medium and large enterprises were examined and a set of hypotheses, regarding their innovation activity, were developed. The results showed that the adoption of Enterprise Resource Planning (ERP), Customer Relationship Management (CRM) and the electronic information exchange between business partners are positively related to firmâ€™s process innovation activity. Moreover, the results revealed that the employment of ICT-qualified employees, investments in ICTs, firm size and longterm relationships with suppliers also played a major role for European manufacturing firms to conduct internal innovations. The paper highlights the fact that the innovation activity of the firms is deeply affected by a number of different factors, both internally and externally.
Self-tuning control of a nonlinear model of combustion instabilities

We present a self-tuning scheme for adapting the parameters of a PI controller proposed by Fung and Yang (1992) for stabilization of a Culick-type model of nonlinear acoustic oscillations in combustion chambers. Our adaptation criterion is Lyapunov-based and its objective is the regulation of nonlinear pressure oscillations to zero. We focus on a two-mode model and first develop a design based on an assumption that the amplitudes of the two modes are available for measurement. Instead of estimating the damping coefficients of each mode (which are dependent on the unknown air/fuel ratio), the Lyapunov approach allows us to adapt the parameters of the controller directly. The adaptation mechanism is designed to stabilize both modes and prevent the phenomenon observed by Billoud, Galland, Huu, and Candel (1992), whose adaptive controller stabilizes the first but (under some conditions) apparently destabilizes the second mode. We also prove that the adaptation mechanism is robust to a time delay inherent to the actuation approach via heat release. In order to avoid requirements for sophisticated sensing of the mode amplitudes needed for feedback, we also develop an adaptation scheme which employs only one pressure sensor. Our approach is based on the idea to use the squares of the pressure and its derivative instead of the squares of the amplitudes of the modes to drive the adaptation. In order for the adaptation scheme to be implementable, it is also necessary to know the control input matrix of the system. Rather than performing a complicated linear ID procedure, we propose a simple nonlinear ID approach that exploits the quadratic character of the nonlinearities and identifies the input matrix from steady-state limit cycle data. Simulations illustrate the capability of the scheme to attenuate limit cycles without the knowledge of the growth coefficients.
Single nucleotide polymorphisms in premature ovarian failure-associated genes in a Chinese Hui population

Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles in individuals <40 years old, and is a major cause of infertility in females. Genetic factors are considered to be responsible for the development of POF, however, the exact pathogenesis remains to be elucidated in the majority of cases. In the present study, the single nucleotide polymorphisms (SNPs) of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), inhibin βB (INHBB) and follicle stimulating hormone receptor (FSHR) genes were investigated, and their association with POF in a Chinese Hui population of the Ningxia Hui Autonomous Region in western China was evaluated. Peripheral blood samples were collected from 63 patients diagnosed with POF (POF group) and 58 normal control individuals (control group), from which the genomic DNA was isolated. The GDF9, BMP15, INHBB and FSHR genes were amplified using polymerase chain reaction assays, and their SNPs were determined by sequencing. In the four SNPs identified across the GDF9 loci, D57Y (169G>T), rs1049127 (546G>A), rs254286 (447C>T) and rs254285 (969C>G), the frequencies of the 546G>A genotype and allele A were significantly higher in the POF group, compared with the normal control group (34.92, vs. 6.90%; P<0.05 and 19.05, vs. 3.23%; P<0.05, repsectively), while no significant differences were observed in the occur rence of the c.447C>T and c.969C>G mutations between the two groups (60.32, vs. 50% and 50.79, vs. 55.17%, repsectively). The c.169G>T mutation within the GDF9 gene was only detected in two patients with POF, and the mutation did not occur in the normal control group. A total of three SNPs were detected within the BMP15 gene, including rs3810682 (−9C>G), rs79377927 (788_789insTCT) and rs17003221 (852C>T), and no significant differences were observed in the frequencies of the 9C>G and 852C>T genotypes between the POF and control groups (7.94, vs. 6.90% and 4.76, vs. 3.45%, respectively). The 788_789insTCT genotype was detected in only two patients with POF. A novel mutation, c.1095C>A, was identified in exon 2 of the INHBB gene, however, no significant difference was found in the occurrence of the mutation between the two groups (30.16, vs. 22.41%; P>0.05). The rs6165 (919G>A) and rs6166 (2039G>A) SNPs were detected in exon 10 of the FSHR gene; however, no significant difference was observed in the genotype frequencies between the two groups (92.06, vs. 91.38% and 96.83, vs. 93.10%, respecrively). These results demonstrated that GDF9 c.169G>T (D57Y), c.546G>A (rs1049127), and BMP15 rs79377927 (788_789insTCT) were associated with POF in the Chinese Hui population.
Affinity monolith preconcentrators for polymer microchip capillary electrophoresis

Developments in biology are increasing demands for rapid, inexpensive, and sensitive biomolecular analysis. In this study, polymer microdevices with monolithic columns and electrophoretic channels were used for biological separations. Glycidyl methacrylate‐co‐ethylene dimethacrylate monolithic columns were formed within poly(methyl methacrylate) microchannels by in situ photopolymerization. Flow experiments in these columns demonstrated retention and then elution of amino acids under conditions optimized for sample preconcentration. To enhance analyte selectivity, antibodies were immobilized on monoliths, and subsequent lysozyme treatment blocked nonspecific adsorption. The enrichment capability and selectivity of these affinity monoliths were evaluated by purifying fluorescently tagged amino acids from a mixture containing green fluorescent protein (GFP). Twenty‐fold enrichment and 91% recovery were achieved for the labeled amino acids, with a >25 000‐fold reduction in GFP concentration, as indicated by microchip electrophoresis analysis. These devices should provide a simple, inexpensive, and effective platform for trace analysis in complex biological samples.
Mycobacterium tuberculosis Strains with Highly Discordant Rifampin Susceptibility Test Results

ABSTRACT The objectives of this study were to investigate the origin of highly discordant rifampin (rifampicin) (RMP) drug susceptibility test results obtained for Mycobacterium tuberculosis strains during proficiency testing. Nine Supra-National Tuberculosis Reference Laboratories tested the RMP susceptibilities of 19 selected M. tuberculosis strains, using standard culture-based methods. The strains were classified as definitely resistant (R) (n = 6) or susceptible (S) (n = 2) or probably resistant (PR) (n = 8) or susceptible (PS) (n = 3) based on rpoB mutations and treatment outcome. All methods yielded a susceptible result for the two S and three PS strains lacking an rpoB mutation and a resistant result for one R strain with a Ser531Leu mutation and one PR strain with a double mutation. Although the remaining 12 R and PR strains had rpoB mutations (four Asp516Tyr, three Leu511Pro, two Leu533Pro, one each His526Leu/Ser, and one Ile572Phe), they were all susceptible by the radiometric Bactec 460TB or Bactec 960 MGIT methods. In contrast, only one was susceptible by the proportion method on Löwenstein-Jensen medium and two on Middlebrook 7H10 agar. Low-level but probably clinically relevant RMP resistance linked to specific rpoB mutations is easily missed by standard growth-based methods, particularly the automated broth-based systems. Further studies are required to confirm these findings, to determine the frequency of these low-level-resistant isolates, and to identify technical improvements that may identify such strains.
A Hybrid Line-based Tracking System for Outdoor Environments

We describe a hybrid tracking system for outdoor augmented reality applications in this paper. There are two main contributions of the proposed system: 1) It makes use of naturally occurring line features to recover 6ODF pose; 2) A high precision gyro is used to track 2D lines across frames for large inter-frame motions. The proposed system has been tested for outdoor augmented reality application. The experiments show that the proposed hybrid 2D-2D line tracking algorithm can reduce the need for 3D-2D matching task, and high accuracy is achieved for the pose recovery.
Improved search strategy for interactive predictions in computer-assisted translation

The statistical machine translation outputs are not error-free and in a high quality yet. So in the cases that we need high quality translations we definitely need the human intervention. An interactive-predictive machine translation is a framework, which enables the collaboration of the human and the translation system. Here, we address the problem of searching the best suffix to propose to the user in the phrase-based interactive prediction scenario. By adding the jump operation to the common edit distance based search, we try to overcome the lack of some of the reorderings in the search graph which might be desired by the user. The experiments results shows that this method improves the base method by 1.35% in KSMR 2 , and if we combine the edit error in the proposed method with the translation scores given by the statistical models to select the offered suffix, we could gain the KSMR improvement of about 1.63% compared to the base search method.
Facial ethnicity classification based on boosted local texture and shape descriptions

Ethnicity is a key demographic attribute of human beings and it plays a important role in automatic machine based face analysis, therefore, there has been increasing attention for face based ethnicity classification in recent years. In this paper, we propose a novel method on such an issue by combining both boosted local texture and shape features extracted from 3D face models, in contrast to the existing ones that only depend on 2D facial images. The proposed method makes use of the Oriented Gradient Maps (OGMs) to highlight local geometry as well as texture variations of entire faces, while further learns a compact set of features which are highly related to the ethnicity property for classification. Experiments are comprehensively carried out on the FRGC v2.0 dataset, and the performance is up to 98.3% to distinguish Asians from non-Asians when 80% samples are used in the training set, demonstrating the effectiveness of the proposed method.
No evidence for productive PERV infection of baboon cells in in vivo infection model.

OBJECTIVES The discovery that pig endogenous retroviruses are infectious for human cells in vitro lead to vehement discussions about the possible risk of infection after clinical xenotransplantation. Since PERV transmission to non-human primate cells in vitro has been observed, similar to human cells, infection studies in non-human primates should represent the best model to analyze a potential PERV transmission after xenotransplantation. However, it is still open to discussion, whether non-human primate cells can be infected productively-similar to human cells- and whether those species are suitable to analyze PERV infection risks in vivo. METHODS In vitro, only few cell types can be tested for susceptibility. We developed a pig to baboon cell transplantation model with special emphasis on B-cell effective immunosuppression, removal of anti Gal-alpha 1,3-Gal-antibodies, inhibition of the complement cascade and long term survival of transplanted cellular grafts. This model allows us to investigate in vivo, whether any baboon cell types may be permissive for productive PERV infection. The xenograft recipients were investigated for up to 535 days post transplantation. Gal-alpha 1,3-Gal-antibody and complement levels were monitored. Potential PERV transmission was analyzed, not only in PBMC, but in a variety of tissue samples as well as in serum and plasma samples by PCR, RT-PCR and by detection of RT-activity. Moreover, potential PERV specific immune responses were studied by a highly sensitive Western-Blot-assay. RESULTS Despite several days of extremely low levels of Gal-alpha 1,3-Gal-antibody and complement, and despite of long term xenochimerism, no evidence for PERV infection was obtained in any of the tested tissues or in the tested serum samples. CONCLUSION This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.