Miracle-dz/UniFAR-FTUs huggingface dataset:
Elucidating a false-negative MYC break-apart fluorescence in situ hybridization probe study by next-generation sequencing in a patient with high-grade B-cell lymphoma with IGH/MYC and IGH/BCL2 rearrangements

The identification of MYC rearrangements in several mature B-cell neoplasms is critical for diagnostic and prognostic purposes. Commercially available fluorescence in situ hybridization (FISH) probe sets, including IGH/MYC dual-color dual-fusion (D-FISH) and MYC break-apart probes (BAPs), serve as the primary methodology utilized to detect MYC rearrangements. However, performing either IGH/MYC D-FISH or MYC BAP FISH studies in isolation has been reported to result in false-negative results because of the complex nature of 8q24 rearrangements involving the MYC gene region. We report a 60-yr-old male with newly diagnosed high-grade B-cell lymphoma with a negative MYC BAP study, but with positive BCL2 and BCL6 BAP studies. Per our current laboratory algorithm to concurrently interrogate the MYC gene region with both MYC BAP and IGH/MYC D-FISH probe sets, we performed IGH/MYC D-FISH studies and detected an IGH/MYC fusion. To further characterize the discrepant MYC results obtained by FISH, a next-generation sequencing strategy, mate-pair sequencing (MPseq), was performed and revealed a small insertion (∼200 kb) of the IGH locus downstream from the MYC gene that was undetectable by MYC BAP studies. This case highlights the importance of utilizing both IGH/MYC D-FISH and MYC BAP sets to detect potential cryptic MYC rearrangements and also demonstrates the power of MPseq to characterize complex structural rearrangements and copy-number abnormalities unappreciable by FISH.
Corepressor-Directed Preacetylation of Histone H3 in Promoter Chromatin Primes Rapid Transcriptional Switching of Cell-Type-Specific Genes in Yeast

ABSTRACT Switching between alternate states of gene transcription is fundamental to a multitude of cellular regulatory pathways, including those that govern differentiation. In spite of the progress in our understanding of such transitions in gene activity, a major unanswered question is how cells regulate the timing of these switches. Here, we have examined the kinetics of a transcriptional switch that accompanies the differentiation of yeast cells of one mating type into a distinct new cell type. We found that cell-type-specific genes silenced by the α2 repressor in the starting state are derepressed to establish the new mating-type-specific gene expression program coincident with the loss of α2 from promoters. This rapid derepression does not require the preloading of RNA polymerase II or a preinitiation complex but instead depends upon the Gcn5 histone acetyltransferase. Surprisingly, Gcn5-dependent acetylation of nucleosomes in the promoters of mating-type-specific genes requires the corepressor Ssn6-Tup1 even in the repressed state. Gcn5 partially acetylates the amino-terminal tails of histone H3 in repressed promoters, thereby priming them for rapid derepression upon loss of α2. Thus, Ssn6-Tup1 not only efficiently represses these target promoters but also functions to initiate derepression by creating a chromatin state poised for rapid activation.
Communication between distinct subunit interfaces of the cohesin complex promotes its topological entrapment of DNA

Cohesin mediates higher-order chromosome structure. Its biological activities require topological entrapment of DNA within a lumen(s) formed by cohesin subunits. The reversible dissociation of cohesin’s Smc3p and Mcd1p subunits are postulated to form a regulated gate that allows DNA entry and exit into the lumen. We assessed gate-independent functions of this interface in yeast using a fusion protein that joins Smc3p to Mcd1p. We show that in vivo all the regulators of cohesin promote DNA binding of cohesion by mechanisms independent of opening this gate. Furthermore, we show that this interface has a gate-independent activity essential for cohesin to bind chromosomes. We propose this interface regulates DNA entrapment by controlling the opening and closing of one or more distal interfaces formed by cohesin subunits, likely by inducing a conformation change in cohesin. Furthermore, cohesin regulators modulate the interface to control both DNA entrapment and cohesin functions after DNA binding.
Sin mutations of histone H3: influence on nucleosome core structure and function

Sin mutations in Saccharomyces cerevisiae alleviate transcriptional defects that result from the inactivation of the yeast SWVI/SNF complex. We have investigated the structural and functional consequences for the nucleosome of Sin mutations in histone H3. We directly test the hypothesis that mutations in histone H3 leading to a SWI/SNF-independent (Sin) phenotype in yeast lead to nucleosomal destabilization. In certain instances this is shown to be true; however, nucleosomal destabilization does not always occur. Topoisomerase I-mediated relaxation of minichromosomes assembled with either mutant histone H3 or wild-type H3 together with histones H2A, H2B, and H4 indicates that DNA is constrained into nucleosomal structures containing either mutant or wild-type proteins. However, nucleosomes containing particular mutant H3 molecules (R116-H and T118-I) are more accessible to digestion by micrococcal nuclease and do not constrain DNA in a precise rotational position, as revealed by digestion with DNase I. This result establishes that Sin mutations in histone H3 located close to the dyad axis can destabilize histone-DNA contacts at the periphery of the nucleosome core. Other nucleosomes containing a distinct mutant H3 molecule (E105-K) associated with a Sin phenotype show very little change in nucleosome structure and stability compared to wild-type nucleosomes. Both mutant and wild-type nucleosomes continue to restrict the binding of either TATA-binding protein/transcription factor IIA (TFIIA) or the RNA polymerase III transcription machinery. Thus, different Sin mutations in histone H3 alter the stability of histone-DNA interactions to various extents in the nucleosome while maintaining the fundamental architecture of the nucleosome and contributing to a common Sin phenotype.
Effects of Lycopene in Hyperoxia-Induced Lung Injury in Newborn Rats.

The aim of this study was to evaluate the therapeutic effect of lycopene on a hyperoxia-induced lung injury model in rat pups. Full-term rat pups were included in the study 12-24 h after delivery. The pups were separated into 4 groups: normoxia control (NC), hyperoxia control (HC), hyperoxia + lycopene (HL), and normoxia lycopene (NL). The normoxia groups were housed in ambient air, and the hyperoxia groups in > 85% O2. HL and NL groups received 50 mg lycopene in oil/kg body weight/day delivered intraperitoneally (i.p.), the other groups received oil alone. On day 11, the rat pups were sacrificed and their lungs removed. Statistically significant injury was observed in all histological parameters measured (MLI, proliferating cell nuclear antigen (PCNA), and apoptosis) in the HC group (HC vs NC, p = 0.001). This injury could not be reversed with lycopene treatment (HC vs HL, 0.05; NC vs HL, p = 0.001). With hyperoxia, statistically significant decreases were observed in biochemical parameters in terms of SOD, MDA, and IL-6 values (HC vs NC: SOD, p = 0.02; MDA, p = 0.043; IL-6, p = 0.001). The use of lycopene did not provide any improvement in these values (HC vs HL, p > 0.05). Hyperoxia or lycopene had no effect on IL-1β and GPx (p > 0.05). When comparing NC and NL groups, negative effects were observed in the group given lycopene in terms of MLI, PCNA, apoptosis, and IL-6 (all parameters, p = 0.001). We observed that 50 mg lycopene in oil/kg body weight/day given via i.p. had no curative effect on the hyperoxia-induced lung injury in newborn rats and may even induce adverse effects.
Theoretical results on the effect of ‘shortcut’ actions in MDPs

Temporally extended actions have been used extensively in reinforcement learning in order to speed up the process of learning good behaviours. While such actions are intuitively appealing, very little work has provided a formal analysis of the advantage that can be obtained by using such actions. In this paper, we tackle this problem using the methodology of stochastic processes. We present case studies of Markov decision processes with actions that allow ‘shortcuts’ between different parts of the environment, and show how such actions affect the travel time between states. Our main finding is that such actions allow for provably quicker travel around the environment, and the benefit increases with the dimensionality of the state space. Hence, extended actions help in efficiently exploring large, high-dimensional domains.
NiS2@rGO Nanosheet Wrapped with PPy Aerogel: A Sandwich-Like Structured Composite for Excellent Microwave Absorption

To reduce electromagnetic pollution as well as increase the accuracy of high-precision electronic equipment, more attention has been paid to new electromagnetic wave (EMW) absorbing materials, which have the advantages of strong absorption, wide absorption bands, and a narrow thickness. In this study, a novel ternary type of the NiS2@rGO/polypyrrole (PPy) sandwich-like structured composites was synthesized via a facile two-step method, in which the hydrothermal method was used to prepare NiS2@rGO binary composites and then the in situ polymerization method was used to synthesize the PPy, which acted as the outer layer of the sandwich-like structure. The morphologies and electromagnetic absorption performance of the NiS2@rGO/PPy were measured and investigated. A sample with 6 wt% NiS2@rGO/PPy loading paraffin-composite obtained an outstanding reflection loss (RL) of −58.7 dB at 16.44 GHz under a thickness of 2.03 mm. Simultaneously, the effective electromagnetic wave absorption bandwidth for RL < −10 dB, which covered 7.04 to 18.00 GHz (10.96 GHz), was achieved by changing the thickness of the absorber from 2.0 to 3.5 mm. The results not only suggest that the NiS2@rGO/PPy composite has excellent performance in the field of EMW absorption but also prove that the novel sandwich-like structure can contribute to appropriate impedance matching through multiple relaxation and interfacial polarization processes.
Hidden genomic evolution in a morphospecies—The landscape of rapidly evolving genes in Tetrahymena

A morphospecies is defined as a taxonomic species based wholly on morphology, but often morphospecies consist of clusters of cryptic species that can be identified genetically or molecularly. The nature of the evolutionary novelty that accompanies speciation in a morphospecies is an intriguing question. Morphospecies are particularly common among ciliates, a group of unicellular eukaryotes that separates 2 kinds of nuclei—the silenced germline nucleus (micronucleus [MIC]) and the actively expressed somatic nucleus (macronucleus [MAC])—within a common cytoplasm. Because of their very similar morphologies, members of the Tetrahymena genus are considered a morphospecies. We explored the hidden genomic evolution within this genus by performing a comprehensive comparative analysis of the somatic genomes of 10 species and the germline genomes of 2 species of Tetrahymena. These species show high genetic divergence; phylogenomic analysis suggests that the genus originated about 300 million years ago (Mya). Seven universal protein domains are preferentially included among the species-specific (i.e., the youngest) Tetrahymena genes. In particular, leucine-rich repeat (LRR) genes make the largest contribution to the high level of genome divergence of the 10 species. LRR genes can be sorted into 3 different age groups. Parallel evolutionary trajectories have independently occurred among LRR genes in the different Tetrahymena species. Thousands of young LRR genes contain tandem arrays of exactly 90-bp exons. The introns separating these exons show a unique, extreme phase 2 bias, suggesting a clonal origin and successive expansions of 90-bp–exon LRR genes. Identifying LRR gene age groups allowed us to document a Tetrahymena intron length cycle. The youngest 90-bp exon LRR genes in T. thermophila are concentrated in pericentromeric and subtelomeric regions of the 5 micronuclear chromosomes, suggesting that these regions act as genome innovation centers. Copies of a Tetrahymena Long interspersed element (LINE)-like retrotransposon are very frequently found physically adjacent to 90-bp exon/intron repeat units of the youngest LRR genes. We propose that Tetrahymena species have used a massive exon-shuffling mechanism, involving unequal crossing over possibly in concert with retrotransposition, to create the unique 90-bp exon array LRR genes.
Eosinophilic airway inflammation induced by repeated exposure to cigarette smoke.

Acute exposure to cigarette smoke causes airway hyperresponsiveness (AHR) in guinea-pigs, which resolves within a few hours. Repeated exposure may have a different effect on the airways. To address this question, guinea-pigs were repeatedly exposed to cigarette smoke (six cigarettes for 1 h x day(-1)) for 14 consecutive days. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 1 day after the last exposure. Significant neutrophilia in BALF was observed after 3 days of smoke exposure. Significant eosinophilia in BALF and AHR were observed after 14 days of smoke exposure, but not after 3 or 7 days of smoke exposure. These changes persisted until 3 days after the last exposure and resolved 7 days afterwards. Histologically, the recruited eosinophils were observed predominantly in the airways, but not in the alveoli. Treatment with E-6123, a specific platelet-activating factor receptor antagonist (1 mg x kg(-1) x day(-1) p.o. during smoke exposure) significantly inhibited the eosinophil influx and AHR. Repeated exposure to cigarette smoke may induce prolonged airway inflammation and airway hyperresponsiveness in guinea-pigs. Platelet-activating factor or platelet-activating factor-like lipids may play a key role in airway hyperresponsiveness, presumably by the induction of eosinophilic airway inflammation.
Alginate microspheres prepared by ionic crosslinking of pickering alginate emulsions

Abstract Modification of reduced graphene oxide nanosheets (MrGO) is an effective strategy to increase their dispersability and hydrophobicity in order to fabricate alginate microspheres via crosslingking stable Pickering alginate emulsions stabilized by MrGO, in where alginate aqueous solution is the dispersed phase and an organic solvent the continuous phase. The effects of MrGO concentration, water/oil ratio and salt concentration on the alginate spheres were investigated, and the results shows that MrGO could efficiently stabilize alginate spheres in suitable conditions and increasing the MrGO concentration or the oil/water ratio was favorable to the formation of alginate spheres. Using this method, alginate microspheres loaded with drug were easily fabricated and their release properties at different conditions were discussed.
Dynamic Semantics for Tense and Aspect

A semantics for tense, modality, and aspect in natural language must capture causal and contingent relations between events and states as welt as merely temporal ones The paper investigates a non-reified dynamic logic based, formulation of the situation calculus is a formalism for a computational semantics for a number of temporal categories in English and suggests that some recent claims that dynamic logics are inherently unsuitable for this purpose have taken too narrow a view of the situation calculus.
Pattern Classification

In today’s electronic age, it would be nice to have access to the examples: data or program downloads from a web site or a diskette/CD with the book. Software solutions are outlined but not provided. The author uses his own custom APL programs. Exercises are included at the end of each chapter. The author’s intention is to have practitioners consider the kind of problem and kind of data under study, in order to select an appropriate model that will adequately answer the questions of interest. He is correct in stating that this book is for people with experience in survival data and analysis. The book does provide a condensed introductory chapter on univariate survival analysis. He also intends this work to be a toolbox and not a cookbook. This means that the reader should be comfortable with reading mathematical statistics, but siting and proving theorems is not expected, nor is it part of the content. The annotated bibliography at the end of each chapter compliments the chapter material, particularly for those interested in the purely theoretical aspects of the material.
ATR disruption leads to chromosomal fragmentation and early embryonic lethality.

Although a small decrease in survival and increase in tumor incidence was observed in ATR(+/-) mice, ATR(-/-) embryos die early in development, subsequent to the blastocyst stage and prior to 7.5 days p.c. In culture, ATR(-/-) blastocysts cells continue to cycle into mitosis for 2 days but subsequently fail to expand and die of caspase-dependent apoptosis. Importantly, caspase-independent chromosome breaks are observed in ATR(-/-) cells prior to widespread apoptosis, implying that apoptosis is caused by a loss of genomic integrity. These data show that ATR is essential for early embryonic development and must function in processes other than regulation of p53.
A High-Efficiency Voltage Equalization Scheme for Supercapacitor Energy Storage System in Renewable Generation Applications

Due to its fast charge and discharge rate, a supercapacitor-based energy storage system is especially suitable for power smoothing in renewable energy generation applications. Voltage equalization is essential for series-connected supercapacitors in an energy storage system, because it supports the system’s sustainability and maximizes the available cell energy. In this paper, we present a high-efficiency voltage equalization scheme for supercapacitor energy storage systems in renewable generation applications. We propose an improved isolated converter topology that uses a multi-winding transformer. An improved push-pull forward circuit is applied on the primary side of the transformer. A coupling inductor is added on the primary side to allow the switches to operate under the zero-voltage switching (ZVS) condition, which reduces switching losses. The diodes in the rectifier are replaced with metal-oxide-semiconductor field-effect transistors (MOSFETs) to reduce the power dissipation of the secondary side. In order to simplify the control, we designed a controllable rectifying circuit to achieve synchronous rectifying on the secondary side of the transformer. The experimental results verified the effectiveness of the proposed design.
Equations of substrate‐limited growth: The case for blackman kinetics

A simplified model of cell metabolism, consisting of a series of linked reversible enzymatic reactions dependent on the concentration of a single external substrate has been developed. The general mathematical solution for this system of reactions is presented. This general solution confirms the concept of a rate‐limiting step, or “master reaction”, in biological systems as first proposed by Blackman. The maximum rate of such a process is determined by, and equal to, the maximum rate of the slowest forward reaction in the series.
Structural basis for substrate selectivity and nucleophilic substitution mechanisms in human adenine phosphoribosyltransferase catalyzed reaction

The reversible adenine phosphoribosyltransferase enzyme (APRT) is essential for purine homeostasis in prokaryotes and eukaryotes. In humans, APRT (hAPRT) is the only enzyme known to produce AMP in cells from dietary adenine. APRT can also process adenine analogs, which are involved in plant development or neuronal homeostasis. However, the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction remains poorly understood. Here we present the crystal structures of hAPRT complexed to three cellular nucleotide analogs (hypoxanthine, IMP, and GMP) that we compare with the phosphate-bound enzyme. We established that binding to hAPRT is substrate shape–specific in the forward reaction, whereas it is base-specific in the reverse reaction. Furthermore, a quantum mechanics/molecular mechanics (QM/MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (SN2) with a mix of SN1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted SN2-type mechanism would be involved in the reverse reaction. These results provide a framework for understanding the molecular mechanism and substrate discrimination in both directions by APRTs. This knowledge can play an instrumental role in the design of inhibitors, such as antiparasitic agents, or adenine-based substrates.
GaN technologies and developments: Status and trends

Today the European GaN interest is slightly shifting away from academic research to development and industrialization of technology, devices and applications. The recent public funding was started to accelerate the transition from academica to industry on all levels like EC, national and by Space Agencies. In the paper the today's running projects and the upcoming trends will be described.
Towards a Computationally Efficient Relative Positioning System for Indoor Environments - An RFID Approach

The recent advancements of Radio Frequency IDentification (RFID)-based localization approach has necessitates the development of effective solutions for mobile robot navigation systems in an indoor and/or outdoor environment. Among the most common problems pertaining to the modern RFID-based robot navigation systems are that multiple reference RF stations or excessive number of sensors are utilized for the location sensing with RFID, however, particularly in indoor environments, spatial layout or cost problems limit the applicability of those approaches. The contribution of the current manuscript is to devise a simple computationally efficient relative positioning system for indoor environments through a modified RFID tag architecture. The validity of the proposed RFID-based RPS is demonstrated using the real data collected in a typical indoor environment. NOMENCLATURE N Total number of RFID tags p̂ Estimated robot position p True robot position pi Position of tag i ê Robot position error ∆RSS Received signal strength difference RSSi Average RSS value of tag i RSS ji jth RSS value of tag i
Phylogenetic relationships among the clownfish-hosting sea anemones

The clownfish-sea anemone symbiosis has been a model system for understanding fundamental evolutionary and ecological processes. However, our evolutionary understanding of this symbiosis comes entirely from studies of clownfishes. A holistic understanding of a model mutualism requires systematic, biogeographic, and phylogenetic insight into both partners. Here, we conduct the largest phylogenetic analysis of sea anemones (Order Actiniaria) to date, with a focus on expanding the biogeographic and taxonomic sampling of the 10 nominal clownfish-hosting species. Using a combination of mtDNA and nuDNA loci we test 1) the monophyly of each clownfish-hosting family and genus, 2) the current anemone taxonomy that suggests symbioses with clownfishes evolved multiple times within Actiniaria, and 3) whether, like the clownfishes, there is evidence that host anemones have a Coral Triangle biogeographic origin. Our phylogenetic reconstruction demonstrates widespread poly-and para-phyly at the family and genus level, particularly within the family Stichodactylidae and genus Sticodactyla, and suggests that symbioses with clownfishes evolved minimally three times within sea anemones. We further recover evidence for a Tethyan biogeographic origin for some clades. Our data provide the first evidence that clownfish and some sea anemone hosts have different biogeographic origins, and that there may be cryptic species of host anemones. Finally, our findings reflect the need for a major taxonomic revision of the clownfish-hosting sea anemones.