Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleosome conformational variability in solution and in interphase nuclei evidenced by cryo-electron microscopy of vitreous sections

In Eukaryotes, DNA is wound around the histone core octamer to form the basic chromatin unit, the nucleosome. Atomic resolution structures have been obtained from crystallography and single particle cryo-electron microscopy of identical engineered particles. But native nucleosomes are dynamical entities with diverse DNA sequence and histone content, and little is known about their conformational variability, especially in the cellular context. Using cryo-electron microscopy and tomography of vitreous sections we analyse the conformation of native nucleosomes, both in vitro, using purified particles solubilised at physiologically relevant concentrations (25-50 %), and in situ, within interphase nuclei. We visualise individual nucleosomes at a level of detail that allows us to analyse the conformation of the DNA wrapped around, and measure the distance between the DNA gyres. We evidence a variety of conformations. In interphase nuclei open nucleosomes predominate, with an average inter-gyre distance larger than that of the canonical particle. In concentrated solutions, we evidence a salt–dependant transition, with high salt compact conformations resembling the canonical nucleosome, and open low salt ones, closer to nuclear nucleosomes. Although further particle characterisation and cartography are needed to understand the relationship between this conformational variability and chromatin functional states, this work opens a route to chromatin exploration in situ.
Integration of gaze and gesture detection in nature language instructing of robot in an assembly scenario

We present the development of and experiments with a robot system showing multimodal interaction capabilities. We focus on the understanding of human instructions in natural language by integrating gaze and pointing hand gestures. A typical application of such a system is interactive assembly. A human communicator sharing a view of the assembly scenario with the robot instructs the latter by speaking to it in the same way that he would communicate with a child. His instructions can be under-specified, incomplete and/or context-dependent. By detecting gaze and gesture information of the instructor, which are described in two sections of the paper, the ambiguities in the interactions can be resolved in a natural manner. Finally, we outline a list of future topics for extending our research.
Feedback directed optimization in Compaq's compilation tools for Alpha

This paper describes and evaluates the feedback directed optimizations that are used in the Compaq C compiler tool chain for Alpha. The optimizations include superblock formation, inlining, commando loop optimization, register allocation, code layout, and switch statement optimization. The optimizations either are extensions of classical optimizations or are restructuring transformations that enable classical optimizations. Feedback directed optimization is highly effective, achieving a 17% speedup over aggressive classical optimization. Inlining contributes the most performance and code layout, superblock formation, and loop restructuring are also important.
Study on Image Retargeting Methods in View of Importance-Map

This paper analyzes the characteristics of the state-of-the-art technologys with regard to content-aware image retargeting in detail, contrasts the merits and demerits between diverse technologys, and lists the performance and effect about each method. The primary processes of content-aware image retargeting are divided into two steps: first step is the recognition of image importance-map, which is generally generated by the combination of image gradient and visual significance, indicates that human eyes generates diverse sensitivity of watching different area in image; Current papers with respect to content-aware image retargeting primarily centers on the resizing method in the second step. In the light of the traits of different ways, this article subdivided the technologys into three categories: on account of seam-carving, image-deformation and multi-operator. At last, we give the final qualitative analysis about the three algorithms mentioned above.
Prevalence of subclinical ketosis and production diseases in dairy cows in Central and South America, Africa, Asia, Australia and New Zealand, and Eastern Europe

Subclinical ketosis (SCK) and periparturient diseases considerably account for economic and welfare losses in dairy cows. The majority of scientific reports investigating the prevalence of SCK and production diseases are based on empirical studies conducted in Western Europe and North America. The present study surveyed the prevalence of SCK and production-related clinical diseases in early lactating cows in various countries across the world other than those in North America and Western Europe. Twelve countries of South and Central America (Argentina, Brazil, Chile, Colombia, Mexico), Africa (South Africa), Asia (Thailand, China), Eastern Europe (Russia, Ukraine), Australia and New Zealand were assessed, and data from a total of 8,902 cows kept at 541 commercial dairy farms were obtained. A minimum of 5 cows per farm were blood sampled and examined once after parturition up to day 21 of lactation. Blood concentration of β-hydroxybutyrate (BHBA) was measured (threshold for SCK: 1.2 mmol/l) and the presence of production-related diseases such as milk fever, retained placenta, mastitis, metritis, displaced abomasum, claw disease and clinical ketosis was recorded. More than 95% of all cows were examined in their second week of lactation. Across all investigated countries, the SCK prevalence was 24.1%, ranging from 8.3% up to 40.1%. The prevalence of production-related diseases detected during the first 21 days of lactation was relatively low (
Detecting Differential Variable microRNAs via Model-Based Clustering

Identifying genomic probes (e.g., DNA methylation marks) is becoming a new approach to detect novel genomic risk factors for complex human diseases. The F test is the standard equal-variance test in Statistics. For high-throughput genomic data, the probe-wise F test has been successfully used to detect biologically relevant DNA methylation marks that have different variances between two groups of subjects (e.g., cases vs. controls). In addition to DNA methylation, microRNA is another mechanism of epigenetics. However, to the best of our knowledge, no studies have identified differentially variable (DV) microRNAs. In this article, we proposed a novel model-based clustering to improve the power of the probe-wise F test to detect DV microRNAs. We imposed special structures on covariance matrices for each cluster of microRNAs based on the prior information about the relationship between variance in cases and variance in controls and about the independence among cases and controls. To the best of our knowledge, the proposed method is the first clustering algorithm that aims to detect DV genomic probes. Simulation studies showed that the proposed method outperformed the probe-wise F test and had certain robustness to the violation of the normality assumption. Based on two real datasets about human hepatocellular carcinoma (HCC), we identified 7 DV-only microRNAs (hsa-miR-1826, hsa-miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR-99b) using the proposed method, one (hsa-miR-1826) of which has not yet been reported to relate to HCC in the literature.
Whole Exome Sequencing in 20,197 Persons for Rare Variants in Alzheimer Disease

Objective The genetic bases of Alzheimer’s disease remain uncertain. An international effort to fully articulate genetic risks and protective factors is underway with the hope of identifying potential therapeutic targets and preventive strategies. The goal here was to identify and characterize the frequency and impact of rare and ultra-rare variants in Alzheimer’s disease using whole exome sequencing in 20,197 individuals. Methods We used a gene-based collapsing analysis of loss-of-function ultra-rare variants in a case-control study design with data from the Washington Heights-Inwood Columbia Aging Project, the Alzheimer’s Disease Sequencing Project and unrelated individuals from the Institute of Genomic Medicine at Columbia University. Results We identified 19 cases carrying extremely rare SORL1 loss-of-function variants among a collection of 6,965 cases and a single loss-of-function variant among 13,252 controls (p = 2.17 × 10-8; OR 36.2 [95%CI 5.8 – 1493.0]). Age-at-onset was seven years earlier for patients with SORL1 qualifying variant compared with non-carriers. No other gene attained a study-wide level of statistical significance, but multiple top-ranked genes, including GRID2IP, WDR76 and GRN, were among candidates for follow-up studies. Interpretation This study implicates ultra-rare, loss-of-function variants in SORL1 as a significant genetic risk factor for Alzheimer’s disease and provides a comprehensive dataset comparing the burden of rare variation in nearly all human genes in Alzheimer’s disease cases and controls. This is the first investigation to establish a genome-wide statistically significant association between multiple extremely rare loss-of-function variants in SORL1 and Alzheimer’s disease in a large whole-exome study of unrelated cases and controls.
Identification of reference genes for real-time PCR gene expression studies during seed development and under abiotic stresses in Cyamopsis tetragonoloba (L.) Taub

Guar (Cyamopsis tetragonoloba) is an important industrial crop. The knowledge about genes of guar involved in various processes can help in developing improved varieties of this crop. qRT-PCR is a preferred technique for accurate quantification of gene expression data. This technique requires the use of appropriate reference genes from the crop to be studied. Such genes have not been yet identified in guar. The expression stabilities of the 10 candidate reference genes, viz., CYP, ACT 11, EF-1α, TUA, TUB, ACT 7, UBQ 10, UBC 2, GAPDH and 18S rRNA were evaluated in various tissues of guar under normal and abiotic stress conditions. Four different algorithms, geNorm, NormFinder, BestKeeper and ∆Ct approach, were used to assess the expression stabilities and the results obtained were integrated into comprehensive stability rankings. The most stable reference genes were found to be CYP and ACT 11(tissues), ACT 11, UBC 2 and ACT 7 (seed development), ACT 7 and TUB (drought stress), TUA, UBC 2 and CYP (nitrogen stress), TUA and UBC 2 (cold stress), GAPDH and ACT 7 (heat stress) and GAPDH and EF-1a (salt stress). These results indicated the necessity of identifying a suitable reference gene for each experimental condition. Four selected reference genes were validated by normalizing the expression of CtMT1 gene. To the best of our knowledge this is the first report on the identification of reference genes in guar. These findings are likely to provide a boost to the gene expression studies in this important crop.
High Performance Histograms on SIMT and SIMD Architectures

Using the histogram procedure, this work studies performance determining factors in computing in parallel on SIMD and SIMT devices. Modern graphics pro-cessing units (GPUs) support SIMT, multiple threads running the same instruction, whereas central processing units (CPUs) use SIMD, in which one instruction op-erates on multiple operands. As part of this work, a cross-technology framework is developed that allows testing a single-source histogram implementation on multiple devices, providing insight into the performance of various API – hardwareconfigurations. It is shown that in the presence of high contention, the implementation of atomic operations becomes of great influence on performance. This work provides guidelines for the choice between devices based on image features and hardware specifications.
Isoform and protein region abnormalities of dysbindin and copper transporter proteins in postmortem schizophrenia substantia nigra

Objective Dysbindin is downregulated in several schizophrenia brain regions and modulates copper transport required for myelination and monoamine metabolism. We sought to determine dysbindin and copper transporter protein expression in schizophrenia subjects. Methods We studied the substantia nigra (which exhibits one of the highest copper contents of the human brain) using Western blot analysis. We characterized specific protein domains of copper transporters ATP7A, CTR1, ATP7B, and dysbindin isoforms 1A and 1B/C in postmortem substantia nigra in schizophrenia subjects (n=15) and matched controls (n=11). As a preliminary investigation, we examined medication status in medicated (n=11) versus unmedicated schizophrenia subjects (n=4). Results The combined schizophrenia group exhibited increased levels of C-terminus, but not N-terminus, ATP7A. Schizophrenia subjects expressed less transmembrane CTR1 and dysbindin 1B/C than controls. When subdivided, the increased C-terminus ATP7A protein was present only in medicated subjects versus controls. Unmedicated subjects exhibited less N-terminus ATP7A protein than controls and medicated subjects, suggesting medication-induced rescue of the ATP7A N-terminus. Transmembrane CTR1 was decreased to a similar extent in both treatment groups versus controls, suggesting no medication effect. Conclusions These results provide the first evidence of disrupted copper transport into and within schizophrenia nigral cells that may be modulated by specific dysbindin isoforms and antipsychotic treatment.
Phylogenomics reveals dynamic evolution of fungal nitric oxide reductases and their relationship to secondary metabolism

Fungi expressing P450nor, an unconventional nitric oxide (NO) reducing cytochrome P450, are thought to be significant contributors to soil nitrous oxide (N2O) emissions. However, fungal contributions to N2O emissions remain uncertain due to inconsistencies in measurements of N2O formation by fungi. Much of the N2O emitted from antibiotic-amended soil microcosms is attributed to fungal activity, yet fungal isolates examined in pure culture are poor N2O producers. To assist in reconciling these conflicting observations and produce a benchmark genomic analysis of fungal denitrifiers, genes underlying fungal denitrification were examined in >700 fungal genomes. Of 167 p450nor–containing genomes identified, 0, 30, and 48 also harbored the denitrification genes narG, napA or nirK, respectively. Compared to napA and nirK, p450nor was twice as abundant and exhibited two to five-fold more gene duplications, losses, and transfers, indicating a disconnect between p450nor presence and denitrification potential. Furthermore, co-occurrence of p450nor with genes encoding NO-detoxifying flavohemoglobins (Spearman r = 0.87, p = 1.6e−10) confounds hypotheses regarding P450nor’s primary role in NO detoxification. Instead, ancestral state reconstruction united P450nor with actinobacterial cytochrome P450s (CYP105) involved in secondary metabolism (SM) and 19 (11 %) p450nor-containing genomic regions were predicted to be SM clusters. Another 40 (24 %) genomes harbored genes nearby p450nor predicted to encode hallmark SM functions, providing additional contextual evidence linking p450nor to SM. These findings underscore the potential physiological implications of widespread p450nor gene transfer, support the novel affiliation of p450nor with fungal SM, and challenge the hypothesis of p450nor’s primary role in denitrification.
Soft-decision interference cancellation for AWGN multi-user channels

This work applies the EM algorithm and a more powerful generalized EM algorithm for ML estimation to the multi-user detection problem. A key feature of the resulting receivers is that they use conditional-mean estimates of the users' bits to reconstruct and cancel multiple-access interference. These soft-decision estimates inherently account for the users SNRs, thereby allowing for effective use of decisions for weaker users in interference cancellation and improving upon the performance of comparable hard-decision-based receivers. <<ETX>>
High affinity interactions and signal transduction between Aβ oligomers and TREM2

Rare coding variant in the Triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased risk for Alzheimer’s disease (AD), but how they confer this risk remains uncertain. We assessed binding of TREM2, AD associated TREM2 variants to various forms of Aβ and APOE in multiple assays. TREM2 interacts directly with various forms of Aβ, with highest affinity interactions observed between TREM2 and soluble Aβ42 oligomers. We confirm the previous interaction between APOE3 and APOE4 and TREM2. High affinity binding of TREM2 to Aβ oligomers is characterized by very slow dissociation. Pre-incubation with Aβ is shown to block the interaction of APOE. In cellular assays, AD-associated variants of TREM2 reduced the amount of Aβ42 internalized, and in NFAT assay the R47H variant decreased NFAT signaling activity in response to Aβ42. These studies demonstrate i) a high affinity interaction between TREM2 and Aβ oligomers that can block interaction with another ligand and ii) that AD-associated TREM2 variants bind Aβ with equivalent affinity but show loss of function in terms of signaling and Aβ internalization.
Concurrent and independent operations to the remote encrypted cloud database from many geographically distributed clients

since data in cloud will be placed anywhere, because of the critical nature of the applications, it is important that clouds be secure. The major security challenge with clouds is that the owner of the data may not have control of where the data is placed. This is because if one wants to exploit the benefits of using cloud computing. This requirement imposes clear data management choices: original plain data must be accessible only by trusted parties that do not include cloud providers, intermediaries, and Internet; in any untrusted context, data must be encrypted. Satisfying these goals has different levels of complexity depending on the type of cloud service. We propose Secure DBaaS as the first solution that allows cloud tenants to take full advantage of DBaaS qualities, such as availability, reliability, and elastic scalability, without exposing unencrypted data to the cloud provider. The architecture design was motivated by goal: to allow multiple, independent, and geographically distributed clients to execute concurrent operations on encrypted data, including SQL statements that modify the database structure. The proposed architecture has the further advantage of eliminating intermediate proxies that limit the elasticity, availability, and scalability properties that are intrinsic in cloud-based solutions. The efficacy of the proposed architecture is evaluated through theoretical analyses and extensive experimental results based on a prototype implementation subject to the TPC-C standard benchmark for different numbers of clients and network latencies.
Genome-Wide DNA Methylation Analysis During Palatal Fusion Reveals the Potential Mechanism of Enhancer Methylation Regulating Epithelial Mesenchyme Transformation.

Epithelial mesenchyme transformation (EMT) of the medial edge epithelium (MEE) is the crucial process during palatal fusion. This work is aimed to elucidate the enhancer regulatory mechanism by genome-wide DNA methylation analysis of EMT during palatal fusion. Over 800 million clean reads, 325 million enzyme reads, and 234 million mapping reads were generated. The mapping rate was 68.85-74.32%, which included differentially methylated 17299 CCGG sites and 2363 CCWGG sites (p < 0.05, log2FC >1). Methylated sites in intron and intergenic regions were more compared to other regions of all DNA elements. GO and KEGG analysis indicated that differential methylation sites related to embryonic palatal fusion genes (HDAC4, TCF7L2, and PDGFRB) at the enhancer were located on CCWGG region of non-CpG islands. In addition, the results showed that the enhancer for HDAC4 was hypermethylated, whereas the enhancers for TCF7L2 and PDGFRB were hypomethylated. The methylation status of enhancer regions of HDAC4, PDGFRB, and TCF7L2, involved in the regulation of the EMT during palatal fusion, may enlighten the development of novel epigenetic biomarkers in the treatment of cleft palate.
Functional plasticity of the gut and the Malpighian tubules underlies cold acclimation and mitigates cold-induced hyperkalemia in Drosophila melanogaster

ABSTRACT At low temperatures, Drosophila, like most insects, lose the ability to regulate ion and water balance across the gut epithelia, which can lead to a lethal increase of [K+] in the hemolymph (hyperkalemia). Cold acclimation, the physiological response to a prior low temperature exposure, can mitigate or entirely prevent these ion imbalances, but the physiological mechanisms that facilitate this process are not well understood. Here, we test whether plasticity in the ionoregulatory physiology of the gut and Malpighian tubules of Drosophila may aid in preserving ion homeostasis in the cold. Upon adult emergence, D. melanogaster females were subjected to 7 days at warm (25°C) or cold (10°C) acclimation conditions. The cold-acclimated flies had a lower critical thermal minimum (CTmin), recovered from chill coma more quickly, and better maintained hemolymph K+ balance in the cold. The improvements in chill tolerance coincided with increased Malpighian tubule fluid secretion and better maintenance of K+ secretion rates in the cold, as well as reduced rectal K+ reabsorption in cold-acclimated flies. To test whether modulation of ion-motive ATPases, the main drivers of epithelial transport in the alimentary canal, mediate these changes, we measured the activities of Na+/K+-ATPase and V-type H+-ATPase at the Malpighian tubules, midgut, and hindgut. Na+/K+-ATPase and V-type H+-ATPase activities were lower in the midgut and the Malpighian tubules of cold-acclimated flies, but unchanged in the hindgut of cold-acclimated flies, and were not predictive of the observed alterations in K+ transport. Our results suggest that modification of Malpighian tubule and gut ion and water transport probably prevents cold-induced hyperkalemia in cold-acclimated flies, and that this process is not directly related to the activities of the main drivers of ion transport in these organs, Na+/K+- and V-type H+-ATPases. Summary: Previous exposure of insects to low temperatures can mitigate cold-induced ion imbalances and improve chill tolerance. Plasticity of ion and fluid transport across the Malpighian tubule and rectal epithelia probably drive this response.