Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunopositivity for Histone MacroH 2 A 1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously. Methods: We examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fatassociated HCC, the high fat diet/diethylnistrosamine (DEN) and the phosphatase and tensin homolog (PTEN) liver specific knock-out (KO) mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry. Results: Protein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (p,0.01) in number of positive nuclei in HCC (100% of tumor cells positive for either macroH2A1.1 or macroH2A1.2), when compared to steatosis (,2% of hepatocytes positive for either isoform). The steatotic areas flanking the tumors were highly immunopositive for macroH2A1.1 and macroH2A1.2. Conclusions: These data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC. Citation: Rappa F, Greco A, Podrini C, Cappello F, Foti M, et al. (2013) Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma. PLoS ONE 8(1): e54458. doi:10.1371/journal.pone. 0054458 Editor: Franco Folli, University of Texas Health Science Center at San Antonio, United States of America Received November 6, 2012; Accepted December 11, 2012; Published January 23, 2013 Copyright: 2013 Rappa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report. Competing Interests: Manlio Vinciguerra is a PLOS ONE Editorial Board member. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: manliovinciguerra@iemest.eu ¤ Current address: Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London, United Kingdom . These authors contributed equally to this work. " These authors also contributed equally to this work
Calcium Leaching Mechanism of Lime Treated Soil Immersed in Seawater

The lime and the cement treated soil have been regarded as stable for a long time due to hydrate generated by pozzolanic reaction. As the treated soil is exposed to natural conditions, its strength would decrease by calcium leaching. In lowland having the thick alluvial clay deposit, the chemical soil treated method is often applied to improve the strength of soft clay ground. The lime treated soil applied to the base of a tidal river dike is deteriorating. It had been constructed in about twenty years ago and now appears to be muddy and leakage of river water. The treated soil is exposed to seawater in this area. This study considered mechanism of calcium leaching from the lime treated soil when it was immersed in seawater. Leaching tests were carried out to clear influences of the component of seawater on calcium leaching. Artificial seawater, NaCl, MgCl2, MgSO4 solutions were used in the test. Influence of NaCl on calcium leaching was very small. Magnesium containing in seawater reduced pH value of the solution-treated soil mixture. Calcium leaching was accelerated when magnesium concentration was higher. Magnesium was founded to be a main component to cause calcium leaching.
More Cat than Cute?: Interpretable Prediction of Adjective-Noun Pairs

The increasing availability of affect-rich multimedia resources has bolstered interest in understanding sentiment and emotions in and from visual content. Adjective-noun pairs (ANP) are a popular mid-level semantic construct for capturing affect via visually detectable concepts such as "cute dog" or "beautiful landscape". Current state-of-the-art methods approach ANP prediction by considering each of these compound concepts as individual tokens, ignoring the underlying relationships in ANPs. This work aims at disentangling the contributions of the »adjectives» and »nouns» in the visual prediction of ANPs. Two specialised classifiers, one trained for detecting adjectives and another for nouns, are fused to predict 553 different ANPs. The resulting ANP prediction model is more interpretable as it allows us to study contributions of the adjective and noun components.
Recent trend in high-speed wireline link design

We are at a historical cross road in technology roadmap where the numbers of objects connected through internet have vastly outnumbered the human network. This network of smart objects, also known as IoT, will shape our life in the next decade and beyond. By 2020, the number of smart objects is expected to reach 100 million sending massive information over internet. To accommodate such user demand, data centers are also evolving both electrical and optical links are adopting complex modulation schemes. Eventually the need for higher speed from the users, service provider and equipment manufacturer motivates the researchers to push the limit of semiconductor device physics and communication theory. Ultimately, the end product is a fully integrated monolithic solution capable of transmitting and receiving terabits of information. Few example of such market driven R & D development efforts are given in Figure 1. While the particular development trend in each company may vary based on their business strategy, one consistent trend is the rapid increase in data rate over time. Figure also includes example work from these efforts and that also capture underline motivating factors:
Efficient Parallel Join Processing Exploiting SIMD in Multi-Thread Environments

SUMMARY In this paper, we study parallel join processing to improve the performance of the merge phase of sort-merge join by integrating all parallelism provided by mainstream CPUs. Modern CPUs support SIMD instruction sets with wider SIMD registers which allows to process multiple data items per each instruction. Thus, we devise an e ﬃ cient parallel join algorithm, called Parallel Merge Join with SIMD instructions ( PMJS ). In our proposed algorithm, we utilize data parallelism by exploiting SIMD instructions. And we also accelerate the performance by avoiding the usage of conditional branch instructions. Furthermore, to take advantage of the multiple cores, our proposed algorithm is threaded in multi-thread environments. In our multi-thread algorithm, to distribute workload evenly to each thread, we devise an e ﬃ cient workload balancing algorithm based on the kernel density estimator which allows to estimate the workload of each thread accurately.
STUDY OF EFFECTS OF POST­COMPRESSION CURING ON KOLLIDON ® SR BASED FLOATING TABLETS

Floating Kollidon® SR (KSR) matrix tablets containing Labetalol HCl (LBT) were developed and evaluated with respect to in vitro drug release and floating behaviour. Kollidon® SR is amorphous polymer having unusual low glass transition temperature of 29 – 31° C. It was therefore the purpose of this research to study the effects of curing of tablets on tablet properties. Kollidon® SR was able to delay LBT release efficiently. PEG 6000 was used as channeling agent which accelerated the drug release by forming pores in the matrix tablets. Post‐compression curing of tablets increased the hardness, decreased the floating lag time and in vitro drug release. Effects of curing on drug release were reduced by increasing the lactose content and by decreasing KSR content.
Assessment of Clinically Suspected Tubercular Lymphadenopathy by Real-Time PCR Compared to Non-Molecular Methods on Lymph Node Aspirates

Background: The diagnosis of tubercular lymphadenitis (TBLN) is challenging. This study assesses the role of diagnostic intervention with real-time PCR in clinically suspected tubercular lymphadenopathy in relation to cytology and microbiological methods. Methods: The cross-sectional study involved 214 patients, and PCR, cytology, and Ziehl-Neelsen (ZN) staining was performed on aspirates. The findings were compared with culture on Lowenstein-Jensen medium. The overall concordance of cytology and PCR, both individually and combined, was calculated. χ2 and Phi values were assessed between cytology, PCR, and culture. Results: A cytological diagnosis of tuberculosis (TB), reactive lymphoid hyperplasia, and suppurative lymphadenitis was made in 71, 112, and 6 patients, respectively. PCR and culture were positive in 40% of the cases. Among the TBLN patients, PCR showed higher positivity in necrosis and culture showed higher positivity in necrotizing granuloma. Positive ZN staining was observed in 29.6% of the TBLN cases, with an overall positivity of 11%. PCR could additionally detect 82 cases missed by ZN staining. The overall concordance rate for either diagnostic modality, i.e., PCR or cytology, was highest (75%), and for PCR alone was 74%. Phi values were observed to be 0.47 between PCR and culture. Conclusion: Real-time PCR for Mycobacterium tuberculosis complex on aspirates offers a definitive and comparable diagnosis of TBLN. Including this approach as the primary investigation in the work-up of TBLN could reduce the burden of TB.
MiR-9-5p and miR-106a-5p dysregulated in CD4+ T-cells of multiple sclerosis patients and targeted essential factors of T helper17/regulatory T-cells differentiation

Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS. Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. Materials and Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor γt (RORγt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools. Results: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 were up-regulated in relapsing and remitting phases of MS, respectively. Conclusion: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis.
Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering

Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side.
Library usage mining in the context of alternative costs: The case of the Municipal Library of Prague

Purpose The behaviour of a library user is based on his ability to evaluate the consumption of library services based on alternative market services. The purpose of this paper is to study the usage behaviour in a public library building in the context of alternative costs instead of a narrow focus on book circulation data. Design/methodology/approach By library usage mining, using associative rules, the authors described the behaviour of library users and identified the typical behaviour during the visits. The authors analyse the results in the context of alternative costs assigned to the visits. Findings The results confirm that some underused services, such as digital services, deliver significantly greater benefit. The frequency of use, the duration of visit and the number of items used are associated with higher alternative costs. There were no significant differences in alternative cost within economic groups (excluding pensioners). This paper identified 41 frequent patterns with different alternative costs. Research limitations/implications The limitation of this study is the fact that data for library usage mining were collected using a questionnaire survey. Practical implications This may be particularly important for both policy makers and library management. The first beneficiaries are donors and patrons, who can learn about the benefit that libraries bring to society. The proposed system for library usage mining also enables managers to promote specific (effective) services, take steps to avoid readers leaving, and improve the adoption of library services. It can also be used to adapt the location of library services. Librarians, especially those who engage in acquisitions, may also use this information in their evidence-based decisions about the design of services. Originality/value So far, there has been no relevant research on the economic aspects of extracted behaviour patterns. Therefore, this study revealed users’ economic preferences using a questionnaire survey that supplemented transaction data. The ability to describe users’ behaviour can provide library management with enough information to realise evidence-based decision making.
Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks

Osteoarthritis is a high‐incidence painful and debilitating disease characterized by progressive degeneration of articular joints, which indicates a breakdown in joint homeostasis favoring catabolic processes. Biomechanical loading, associated with inflammatory and metabolic imbalances of joint, strongly contributes to the initiation and progression of the disease. Obesity is a primary risk factor for disease onset, and mechanical factors increased the risk for disease progression. Moreover, inflammatory mediators, in particular, adipose tissue‐derived cytokines (better known as adipokines) play a critical role linking obesity and osteoarthritis. The present article summarizes the knowledge about the role of adipokines in cartilage and bone function, highlighting their contribution to the imbalance of joint homeostasis and, consequently, pathogenesis of osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:594–604, 2018.
Update of TTD: Therapeutic Target Database

Increasing numbers of proteins, nucleic acids and other molecular entities have been explored as therapeutic targets, hundreds of which are targets of approved and clinical trial drugs. Knowledge of these targets and corresponding drugs, particularly those in clinical uses and trials, is highly useful for facilitating drug discovery. Therapeutic Target Database (TTD) has been developed to provide information about therapeutic targets and corresponding drugs. In order to accommodate increasing demand for comprehensive knowledge about the primary targets of the approved, clinical trial and experimental drugs, numerous improvements and updates have been made to TTD. These updates include information about 348 successful, 292 clinical trial and 1254 research targets, 1514 approved, 1212 clinical trial and 2302 experimental drugs linked to their primary targets (3382 small molecule and 649 antisense drugs with available structure and sequence), new ways to access data by drug mode of action, recursive search of related targets or drugs, similarity target and drug searching, customized and whole data download, standardized target ID, and significant increase of data (1894 targets, 560 diseases and 5028 drugs compared with the 433 targets, 125 diseases and 809 drugs in the original release described in previous paper). This database can be accessed at http://bidd.nus. edu.sg/group/cjttd/TTD.asp.
Defining the Functionally Important Domain and Amino Acid Residues in Mycobacterium tuberculosis Integration Host Factor for Genome Stability, DNA Binding, and Integrative Recombination

ABSTRACT The integration host factor of Mycobacterium tuberculosis (mIHF) consists of a single polypeptide chain, the product of the ihf gene. We previously revealed that mIHF is a novel member of a new class of nucleoid-associated proteins that have important roles in DNA damage response, nucleoid compaction, and integrative recombination. The mIHF contains a region of 86 amino acids at its N terminus, absent from both α- and β-subunits of Escherichia coli IHF. However, the functional significance of an extra 86-amino-acid region in the full-length protein remains unknown. Here, we report the structure/function relationship of the DNA-binding and integrative recombination-stimulating activity of mIHF. Deletion mutagenesis showed that an extra 86-amino-acid region at the N terminus is dispensable; the C-terminal region possesses the sequences essential for its known biological functions, including the ability to suppress the sensitivity of E. coli ΔihfA and ΔihfB cells to DNA-damaging agents, DNA binding, DNA multimerization-circularization, and stimulation of phage L5 integrase-catalyzed integrative recombination. Single and double alanine substitutions at positions Arg170 and Arg171, located at the mIHF DNA-binding site, abrogated its capacity to suppress the sensitivity of E. coli ΔihfA and ΔihfB cells to DNA-damaging agents. The variants encoded by these mutant alleles failed to bind DNA and stimulate integrative recombination. Interestingly, the DNA-binding activity of the mIHF-R173A variant remained largely unaffected; however, it was unable to stimulate integrative recombination, thus revealing a separation-of-function allele of mIHF. The functional and structural characterization of this separation-of-function allele of mIHF could reveal previously unknown functions of IHF. IMPORTANCE The integration host factor of Mycobacterium tuberculosis is a novel nucleoid-associated protein. mIHF plays a vital role in DNA damage response, nucleoid compaction, and integrative recombination. Intriguingly, mIHF contains an extra 86-amino-acid region at its N terminus, absent from both α- and β-subunits of Escherichia coli IHF, whose functional significance is unknown. Furthermore, a triad of arginine residues located at the mIHF-DNA interface have been implicated in a range of its functions. Here, we reveal the roles of N- and C-terminal regions of mIHF and the individual residues in the Arg triad for their ability to provide protection in vivo against DNA damage, bind DNA, and stimulate integrase-catalyzed site-specific recombination.
Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome

Background Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA. Methods The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated. Results MDS patients had shorter interphase TL than normal healthy donors (P<0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P=0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P=0.003, 0.001, 0.005, 0.005, and 0.013, respectively). Conclusions The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS.