Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploiting Existing Modern Transcripts for Historical Handwritten Text Recognition

Existing transcripts for historic manuscripts are a very valuable resource for training models useful for automatic recognition, aided transcription, and/or indexing of the remaining untranscribed parts of these collections. However, these existing transcripts generally exhibit two main problems which hinder their convenience: a) text of the transcripts is seldom aligned with manuscript lines, and b) text often deviate very significantly from what can be seen in the manuscript, either because writing style has been modernized or abbreviations have been expanded, or both. This work presents an analysis of these problems and discusses possible solutions for minimizing human effort needed to adapt existing transcripts in order to render them usable. Empirical results presented show the huge performance gain that can be obtained by adequately adapting the transcripts, thus motivating future development of the proposed solutions.
Evolution of infant nutrition

Homo sapiens has developed during the course of over two million years. The social and physical conditions of life, the availability of milk and infant foods as well as the presence of diseases have all undergone radical transformations from the Stone Age, at first without and then with fire, to the hunter–gatherer, farmer–herder, agricultural and, now, developed societies. These changes in the human environment may have induced modifications in the length of pregnancy, the development of the neonate at birth, the duration of lactation, the composition of breast milk and use of weaning foods and milk substitutes. Darwinian selection for the nutrient, anti-infective and other components of breast milk may have been determined by the effects of nutrition, through genetic variations in milk composition, on the survival of infants and perhaps also on fecundity and disease resistance in later adult life. Today Darwinian selection may no longer be effective in maintaining or modifying human mammary function, because modern hygienic environments, together with the availability of nutritionally adequate breast-milk substitutes, permit infant survival even under conditions of total lactational failure. National and international promulgations strictly control the composition of infant formulas offered as breast-milk substitutes or as weaning foods. These recommendations are modified as beliefs suggest, and research indicates, the effects of nutrients and other factors on the health and well-being of the child. Preliminary observations on child health have often proved valuable in furthering research. Unquestioning acceptance of apparently desirable, but untested, epidemiological associations have led to unexpected but dangerous iatrogenic problems. Recommendations for change cannot safely be made without proper comparisons with present products and procedures under practical conditions. Such tests are time consuming and require protocols of appropriate statistical design and power while still meeting the required sociological and ethical constraints, but are essential to identify possible harmful effects of any proposed change. It is suggested that no novel ingredients should be added, or major changes permitted in any component, until appropriate trials have established the value and safety of the proposed modifications. Breast-feeding is vital to maximize infant survival in developing countries. There are major difficulties in assessing any differences in morbidity and mortality of breast-fed v. artificially reared infants in the developed world. Carefully controlled studies with comparisons of health and well-being, not only in infancy but throughout life, are desirable if the effects of infant nutrition on adult well-being, suggested by epidemiological studies, are to be validated and ultimately applied. There are considerable variations in the composition of breast milk. This variance suggests that it may ultimately be possible to design formulas better able to meet the needs of individual infants than the milk available from the mother's breast.
Effect of d-Lactate on the Physiological Activity of the ArcB Sensor Kinase in Escherichia coli

ABSTRACT The Arc two-component system, comprising the ArcB sensor kinase and the ArcA response regulator, modulates the expression of numerous genes in response to the respiratory growth conditions. Under anoxic growth conditions ArcB autophosphorylates and transphosphorylates ArcA, which in turn represses or activates its target operons. The anaerobic metabolite d-lactate has been shown to stimulate the in vitro autophosphorylating activity of ArcB. In this study, the in vivo effect of d-lactate on the kinase activity of ArcB was assessed. The results demonstrate that d-lactate does not act as a direct signal for activation of ArcB, as previously proposed, but acts as a physiologically significant effector that amplifies ArcB kinase activity.
Differential coupling of KLF 10 to Sin 3-HDAC and PCAF regulates the inducibility of the FOXP 3 gene

Yuning Xiong,* Phyllis A. Svingen,* Olga O. Sarmento, Thomas C. Smyrk, Maneesh Dave, Sahil Khanna, Gwen A. Lomberk, Raul A. Urrutia, and William A. Faubion, Jr. Epigenetics and Chromatin Dynamics Laboratory, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Translational Epigenomic Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota; and Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota
Sustainable Computing: Informatics and Systems Utility maximizing dynamic resource management in an oversubscribed energy-constrained heterogeneous computing system

The need for greater performance in high performance computing systems combined with rising costs of electricity to power these systems motivates the need for energy-efﬁcient resource management. Driven by the requirements of the Extreme Scale Systems Center at Oak Ridge National Laboratory, we address the problem of scheduling dynamically-arriving tasks to machines in an oversubscribed and energy-constrained heterogeneous distributed computing environment. Our goal is to maximize total “utility” earned by the system, where the utility of a task is deﬁned by a monotonically-decreasing function that represents the value of completing that task at different times. To address this problem, we design four energy-aware resource allocation heuristics and compare their performance to heuristics from the literature. For our given energy-constrained environment, we also design an energy ﬁltering technique that helps some heuristics regulate their energy consumption by allowing tasks to only consume up to an estimated fair-share of energy. Extensive sensitivity analyses of the heuristics in environments with different levels of heterogeneity show that heuristics with the ability to balance both energy consumption and utility exhibit the best performance because they save energy for use by future tasks. © 2014 Elsevier Inc. All rights reserved.
Vitamin D status of northern indigenous people of Russia leading traditional and “modernized” way of life

Background Vitamin D status in groups of northern indigenous people of Russia leading close to traditional (seminomadic reindeer herding), post-traditional (in settlements) or “modernized” (in towns) way of life was analysed. Design The survey study groups consisted of 178 Nenets and Komi aged 18–60 living in the Arctic (66–67°N). Urban Komi, Udmurts and Komi-Permiaks (n=150) living in a non-Arctic area (57–61°N) formed a control group. The concentration of serum 25-hydroxyvitamin D (25OHD), as a transport form of vitamin D, was assessed by enzyme immunoassay analysis. Results The group average 25OHD levels in both rural and urban Arctic residents are within the range of values seen in the non-Arctic urban subjects adjusted for season: 39.7–47.7 nmol/l. Abandoning traditional lifestyle associates with lower vitamin D levels in indigenous Arctic people. Mean±standard deviation 25OHD values among Nenets were lower in those living in the administrative centre (a big settlement) with a population of 1,460 (32.2±12.90 nmol/l) than in the residents of small settlements (39.6±14.08 nmol/l), and in reindeer herders (42.4±13.45 nmol/l; p<0.05 in both cases). Komi townspeople had lower 25OHD concentrations (47.7±12.00 nmol/l) than Komi reindeer herders (68.7±25.20; p<0.01). Conclusions The transition from seminomadic to post-traditional and “modernized” way of life has led to a decrease in the consumption of traditional foods among the indigenous people of the Russian Arctic. Our data support the notion that the traditional northern diet promotes healthy vitamin D levels, while adherence to the “western” type of diet correlates with a lower 25OHD concentration.
Systematic Observations of the Slip Pulse Properties of Large Earthquake Ruptures

In earthquake dynamics there are two end member models of rupture: propagating cracks and self‐healing pulses. These arise due to different properties of faults and have implications for seismic hazard; rupture mode controls near‐field strong ground motions. Past studies favor the pulse‐like mode of rupture; however, due to a variety of limitations, it has proven difficult to systematically establish their kinematic properties. Here we synthesize observations from a database of >150 rupture models of earthquakes spanning M7–M9 processed in a uniform manner and show the magnitude scaling properties of these slip pulses indicates self‐similarity. Further, we find that large and very large events are statistically distinguishable relatively early (at ~15 s) in the rupture process. This suggests that with dense regional geophysical networks strong ground motions from a large rupture can be identified before their onset across the source region.
The genomic trajectory of ovarian high grade serous carcinoma is determined in STIC lesions

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as ‘p53 signatures’, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinomas (STIC) lesions, which, in turn, progress into invasive HGSC that readily spread to the ovary and disseminate around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole genome duplication observed in late-stage disease are determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded samples (FFPE) from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of whole genome duplication, arises early in HGSC, and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development.
Bioinformatics Applications Note Genetics and Population Analysis Fastepistasis: a High Performance Computing Solution for Quantitative Trait Epistasis

Motivation: Genome-wide association studies have become widely used tools to study effects of genetic variants on complex diseases. While it is of great interest to extend existing analysis methods by considering interaction effects between pairs of loci, the large number of possible tests presents a significant computational challenge. The number of computations is further multiplied in the study of gene expression quantitative trait mapping, in which tests are performed for thousands of gene phenotypes simultaneously. Results: We present FastEpistasis, an efficient parallel solution extending the PLINK epistasis module, designed to test for epistasis effects when analyzing continuous phenotypes. Our results show that the algorithm scales with the number of processors and offers a reduction in computation time when several phenotypes are analyzed simultaneously. FastEpistasis is capable of testing the association of a continuous trait with all single nucleotide polymorphism (SNP) pairs from 500 000 SNPs, totaling 125 billion tests, in a population of 5000 individuals in 29, 4 or 0.5 days using 8, 64 or 512 processors. Availability: FastEpistasis is open source and available free of charge only for non-commercial users from http://www.vital-it.ch/software/FastEpistasis
Common Codebook Millimeter Wave Beam Design: Designing Beams for Both Sounding and Communication With Uniform Planar Arrays

Fifth generation wireless networks are expected to utilize wide bandwidths available at millimeter wave (mmWave) frequencies for enhancing system throughput. However, the unfavorable channel conditions of mmWave links, such as, higher path loss and attenuation due to atmospheric gases or water vapor, hinder reliable communications. To compensate for these severe losses, it is essential to have a multitude of antennas to generate sharp and strong beams for directional transmission. In this paper, we consider mmWave systems using uniform planar array (UPA) antennas, which effectively place more antennas on a 2-D grid. A hybrid beamforming setup is also considered to generate beams by combining a multitude of antennas using only a few radio frequency chains. We focus on designing a set of transmit beamformers generating beams adapted to the directional characteristics of mmWave links assuming a UPA and hybrid beamforming. We first define ideal beam patterns for UPA structures. Each beamformer is constructed to minimize the mean squared error from the corresponding ideal beam pattern. Simulation results verify that the proposed codebooks enhance beamforming reliability and data rate in mmWave systems.
Inhibition of Acyl-CoA Synthetase Long Chain Isozymes Decreases Multiple Myeloma Cell Proliferation and Causes Mitochondrial Dysfunction

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Acyl-CoA synthetase long-chain family members (ACSLs) convert free long-chain fatty acids into fatty acyl-CoA esters and play key roles in catabolic and anabolic fatty acid metabolism. The Cancer Dependency Map data suggested that ACSL3 and ACSL4 were among the top 25% Hallmark Fatty Acid Metabolism genes that support MM fitness. Here, we show that inhibition of ACSLs in human myeloma cell lines using the pharmacological inhibitor Triascin C (TriC) causes apoptosis and decreases proliferation in a dose– and time-dependent manner. RNA-seq of MM.1S cells treated with TriC for 24 h showed a significant enrichment in apoptosis, ferroptosis, and ER stress. Proteomics of MM.1S cells treated with TriC for 48 h revealed that mitochondrial dysfunction and oxidative phosphorylation were significantly enriched pathways of interest, consistent with our observations of decreased mitochondrial membrane potential and increased mitochondrial superoxide levels. Interestingly, MM.1S cells treated with TriC for 24 h also showed decreased mitochondrial ATP production rates and overall lower cellular respiration. Implications Overall, our data support the hypothesis that suppression of ACSL in human MM cells inhibit their growth and viability, indicating that ACSL proteins may be promising therapeutic targets in treating myeloma progression.
The Pannexin-1 N-terminal Helix Gates a Switch between Ion Conductance and Anandamide Transport

Anandamide is an endovanilloid and endocannabinoid with ligand activity at transient receptor potential vanilloid 1 channels and cannabinoid receptors, respectively. We have reported that block of Pannexin-1 channels in the CA1 hippocampus can increase concentrations of anandamide and induce presynaptic plasticity. It is not known how an ion channel can contribute to clearance of a lipid-derived signalling molecule. Here, we use electrophysiology and imaging of uptake of fluorescent anandamide to determine the structure-function relationship between the ion conduction and anandamide trasporter activities of pannexin-1. Expression of rat, mouse or human pannexin-1 in HEK cells caused a time dependent increase in anandamide uptake by all three orthologs. However, human pannexin-1 had reduced ion conduction. Low concentrations of anandamide augmented uptake of its fluorescent derivative, whereas higher concentrations competed, suggesting that anadamide may facilitate its own transport. Deletion of the N-terminal helix of pannexin-1 and the channel blocker, probenecid, blocked ion conduction but enhanced anandamide transport. In contrast, mutation of pore facing isoleucine 41 caused a gain of function in ion conduction with loss of anandamide transport. We conclude that the pannexin-1 channel is a dual ion channel / anandamide transporter and that these properties are gated by the channels N-terminal helix and likely linked to its presence or absence within the pore lining region.
Slippery sequences stall the 26S proteasome at multiple points along the translocation pathway

In eukaryotes, the ubiquitin-proteasome system is responsible for intracellular protein degradation. Proteins tagged with ubiquitin are recognized by ubiquitin receptors on the 19S regulatory particle (RP) of the 26S proteasome, unfolded, routed through the translocation channel of the RP, and are then degraded in the 20S core particle (CP). Aromatic paddles on the pore-1 loops of the RP’s Rpt subunits grip the substrate and pull folded domains into the channel, thereby unfolding them. The sequence that the aromatic paddles grip while unfolding a substrate is therefore expected to influence the extent of unfolding, and low complexity sequences have been shown to interfere with grip. However, the detailed spatial requirements for grip while unfolding proteins, particularly from the N-terminus, remain unknown. We determined how the location of glycine-rich tracts relative to a folded domain impairs unfolding. We find that, in contrast to a previous report, inserting glycine-rich sequences closer to the folded domain reduced unfolding ability more than positioning them further away. Locations that have the biggest effect on unfolding map onto the regions where the aromatic paddles are predicted to interact with the substrate. Effects on unfolding from locations up to 67 amino acids away from the folded domain suggest that there are additional interactions between the substrate and the proteasome beyond the aromatic paddles that facilitate translocation of the substrate. In sum, this study deepens understanding of the mechanical interactions within the substrate channel by mapping the spacing of interactions between the substrate and the proteasome during unfolding. Importance The proteasome processively unfolds and degrades target proteins in eukaryotes. However, some substrates are prematurely released, and the resulting partially degraded proteins can cause problems for cells and can be linked to neurodegenerative diseases. In this paper, we use a series of substrates that can stall the proteasome during degradation to probe the translocation pathway substrates must traverse during unfolding. We find that multiple points along the translocation pathway are impacted by these slippery substrates.
Coordinated Evolution of Transcriptional and Post-Transcriptional Regulation for Mitochondrial Functions in Yeast Strains

Evolution of gene regulation has been proposed to play an important role in environmental adaptation. Exploring mechanisms underlying coordinated evolutionary changes at various levels of gene regulation could shed new light on how organism adapt in nature. In this study, we focused on regulatory differences between a laboratory Saccharomyces cerevisiae strain BY4742 and a pathogenic S. cerevisiae strain, YJM789. The two strains diverge in many features, including growth rate, morphology, high temperature tolerance, and pathogenicity. Our RNA-Seq and ribosomal footprint profiling data showed that gene expression differences are pervasive, and genes functioning in mitochondria are mostly divergent between the two strains at both transcriptional and translational levels. Combining functional genomics data from other yeast strains, we further demonstrated that significant divergence of expression for genes functioning in the electron transport chain (ETC) was likely caused by differential expression of a transcriptional factor, HAP4, and that post-transcriptional regulation mediated by an RNA-binding protein, PUF3, likely led to expression divergence for genes involved in mitochondrial translation. We also explored mito-nuclear interactions via mitochondrial DNA replacement between strains. Although the two mitochondrial genomes harbor substantial sequence divergence, neither growth nor gene expression were affected by mitochondrial DNA replacement in both fermentative and respiratory growth media, indicating compatible mitochondrial and nuclear genomes between these two strains in the tested conditions. Collectively, we used mitochondrial functions as an example to demonstrate for the first time that evolution at both transcriptional and post-transcriptional levels could lead to coordinated regulatory changes underlying strain specific functional variations.
Sulfur trioxide formation/emissions in coal-fired air- and oxy-fuel combustion processes: a review

In oxy-fuel combustion, fuel is burned using oxygen together with recycled flue gas which is needed to control the combustion temperature. This leads to higher concentrations of sulfur dioxide and sulfur trioxide in the recycled gas that can result in the formation of sulfuric acid and enhanced corrosion. Current experimental data on SO3 formation, reaction mechanisms, and mathematical modelling have indicated significant differences in SO3 formation between airand oxy-fuel combustion for both the wet and dry flue gas recycle options. This paper provides an extensive review of sulfur trioxide formation in airand oxy-fuel combustion environments, with an emphasis on coal-fired systems. The first part summarizes recent findings on oxy-fuel combustion experiments, as they affect sulfur trioxide formation. In the second part, the review focuses on sulfur trioxide formation mechanisms, and the influence of catalysis on sulfur trioxide formation. Finally, the current methods for measuring sulfur trioxide concentration are also reviewed along with the major difficulties associated with those measurements using data available from both benchand pilot-scale units.