Miracle-dz/UniFAR-FTUs huggingface dataset:
Composition of Glycosaminoglycans in Elasmobranchs including Several Deep-Sea Sharks: Identification of Chondroitin/Dermatan Sulfate from the Dried Fins of Isurus oxyrinchus and Prionace glauca

Shark fin, used as a food, is a rich source of glycosaminoglyans (GAGs), acidic polysaccharides having important biological activities, suggesting their nutraceutical and pharmaceutical application. A comprehensive survey of GAGs derived from the fin was performed on 11 elasmobranchs, including several deep sea sharks. Chondroitin sulfate (CS) and hyaluronic acid (HA) were found in Isurus oxyrinchus, Prionace glauca, Scyliorhinus torazame, Deania calcea, Chlamydoselachus anguineus, Mitsukurina owatoni, Mustelus griseus and Dasyatis akajei, respectively. CS was only found from Chimaera phantasma, Dalatias licha, and Odontaspis ferox, respectively. Characteristic disaccharide units of most of the CS were comprised of C- and D-type units. Interestingly, substantial amount of CS/dermatan sulfate (DS) was found in the dried fin (without skin and cartilage) of Isurus oxyrinchus and Prionace glauca. 1H-NMR analysis showed that the composition of glucuronic acid (GlcA) and iduronic acid (IdoA) in shark CS/DS was 41.2% and 58.8% (Isurus oxyrinchus), 36.1% and 63.9% (Prionace glauca), respectively. Furthermore, a substantial proportion of this CS/DS consisted of E-, B- and D-type units. Shark CS/DS stimulated neurite outgrowth of hippocampal neurons at a similar level as DS derived from invertebrate species. Midkine and pleiotrophin interact strongly with CS/DS from Isurus oxyrinchus and Prionace glauca, affording Kd values of 1.07 nM, 6.25 nM and 1.70 nM, 1.88 nM, respectively. These results strongly suggest that the IdoA-rich domain of CS/DS is required for neurite outgrowth activity. A detailed examination of oligosaccharide residues, produced by chondroitinase ACII digestion, suggested that the IdoA and B-type units as well as A- and C-type units were found in clusters in shark CS/DS. In addition, it was discovered that the contents of B-type units in these IdoA-rich domain increased in a length dependent manner, while C- and D-type units were located particularly in the immediate vicinity of the IdoA-rich domain.
Claudin-4 Expression is Associated With Survival in Ovarian Cancer But Not With Chemotherapy Response

The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson &khgr;2 test. A dataset of >1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1–2.5), P=0.020 and HR=1.6 (1.0–2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0–2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1–1.5), P<0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7–2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.
System Service Call-oriented Symbolic Execution of Android Framework with Applications to Vulnerability Discovery and Exploit Generation

Android Application Framework is an integral and foundational part of the Android system. Each of the 1.4 billion Android devices relies on the system services of Android Framework to manage applications and system resources. Given its critical role, a vulnerability in the framework can be exploited to launch large-scale cyber attacks and cause severe harms to user security and privacy. Recently, many vulnerabilities in Android Framework were exposed, showing that it is vulnerable and exploitable. However, most of the existing research has been limited to analyzing Android applications, while there are very few techniques and tools developed for analyzing Android Framework. In particular, to our knowledge, there is no previous work that analyzes the framework through symbolic execution, an approach that has proven to be very powerful for vulnerability discovery and exploit generation. We design and build the first system, Centaur, that enables symbolic execution of Android Framework. Due to some unique characteristics of the framework, such as its middleware nature and extraordinary complexity, many new challenges arise and are tackled in Centaur. In addition, we demonstrate how the system can be applied to discovering new vulnerability instances, which can be exploited by several recently uncovered attacks against the framework, and to generating PoC exploits.
MYOC and FOXC1 gene analysis in primary congenital glaucoma

Purpose To screen the myocilin (MYOC) and forkhead box protein C1 (FOXC1) genes for sequence variations in primary congenital glaucoma (PCG). Methods Seventy five PCG patients were screened for MYOC variations and 54 cases (negative or heterozygous for cytochrome P4501B1 mutations) for FOXC1 mutations by polymerase chain reaction (PCR) and DNA sequencing. Results Five single nucleotide polymorphisms (SNPs; −126T>C, −83G>A, p.R76K, IVS2+35G>A, and p.Y347Y) were identified in MYOC and two sequence variations (GGC375ins and GGC447ins) in FOXC1. No pathogenic variations were identified in MYOC and FOXC1 in our patients. Conclusions MYOC and FOXC1 mutations are not involved in pathogenesis of primary congenital glaucoma in our patients. Thus, it is important to screen other loci for involvement in congenital glaucoma in cases which are negative or heterozygous for CYP1B1 mutations to have a better insight in to disease pathogenesis.
The CCR4 and CAF1 Proteins of the CCR4-NOT Complex Are Physically and Functionally Separated from NOT2, NOT4, and NOT5

ABSTRACT The CCR4-NOT complex (1 mDa in size), consisting of the proteins CCR4, CAF1, and NOT1 to NOT5, regulates gene expression both positively and negatively and is distinct from other large transcriptional complexes in Saccharomyces cerevisiae such as SNF/SWI, TFIID, SAGA, and RNA polymerase II holoenzyme. The physical and genetic interactions between the components of the CCR4-NOT complex were investigated in order to gain insight into how this complex affects the expression of diverse genes and processes. The CAF1 protein was found to be absolutely required for CCR4 association with the NOT proteins, and CCR4 and CAF1, in turn, physically interacted with NOT1 through its central amino acid region from positions 667 to 1152. The NOT3, NOT4, and NOT5 proteins had no significant effect on the association of CCR4, CAF1, and NOT1 with each other. In contrast, the NOT2, NOT4, and NOT5 interacted with the C-terminal region (residues 1490 to 2108) of NOT1 in which NOT2 and NOT5 physically associated in the absence of CAF1, NOT3, and NOT4. These and other data indicate that the physical ordering of these proteins in the complex is CCR4-CAF1-NOT1-(NOT2, NOT5), with NOT4 and NOT3 more peripheral to NOT2 and NOT5. The physical separation of CCR4 and CAF1 from other components of the CCR4-NOT complex correlated with genetic analysis indicating partially separate functions for these two groups of proteins. ccr4or caf1 deletion suppressed the increased 3-aminotriazole resistance phenotype conferred by not mutations, resulted in opposite effects on gene expression as compared to severalnot mutations, and resulted in a number of synthetic phenotypes in combination with not mutations. These results define the CCR4-NOT complex as consisting of at least two physically and functionally separated groups of proteins.
3D printing in neurosurgery: A systematic review

Background: The recent expansion of three-dimensional (3D) printing technology into the field of neurosurgery has prompted a widespread investigation of its utility. In this article, we review the current body of literature describing rapid prototyping techniques with applications to the practice of neurosurgery. Methods: An extensive and systematic search of the Compendex, Scopus, and PubMed medical databases was conducted using keywords relating to 3D printing and neurosurgery. Results were manually screened for relevance to applications within the field. Results: Of the search results, 36 articles were identified and included in this review. The articles spanned the various subspecialties of the field including cerebrovascular, neuro-oncologic, spinal, functional, and endoscopic neurosurgery. Conclusions: We conclude that 3D printing techniques are practical and anatomically accurate methods of producing patient-specific models for surgical planning, simulation and training, tissue-engineered implants, and secondary devices. Expansion of this technology may, therefore, contribute to advancing the neurosurgical field from several standpoints.
Impact of the Normal Zone Propagation Velocity of High-Temperature Superconducting Coated Conductors on Resistive Fault Current Limiters

The engineering critical current, i.e., Ic, of high-temperature superconducting coated conductors (HTS-CCs), today available on the market, is not a uniform parameter and varies significantly along the length of the conductors. In addition, commercial HTS-CCs have a low normal zone propagation velocity (NZPV). This property, together with the Ic inhomogeneity, exposes the HTS-CCs to local thermal instabilities. A crucial challenge for the design of resistive fault current limiters (RFCLs) based on HTS-CCs is to avoid the thermal runaway of the conductors; and in this respect, the enhancement of the NZPV is a promising solution. In recent years, several methods have been proposed, and many various techniques are now available. In this paper, we are interested to quantify the impact the enhancement of NZPV will have on the design of RFCLs based on HTS-CCs whichever is the adopted technical solution. For this reason, we use numerical models to analyze the effects of the NZPV enhancement on the limitation performance of an RFCL integrated in a medium-voltage power grid.
Understanding the genetic consequences of environmental toxicant exposure: Chernobyl as a model system

We sampled vole populations in Ukraine with the dual goal of characterizing population diversity and of providing a biogeographic perspective to evaluate experimental designs used for previous studies. Our data indicate that genetic diversity in bank vole populations is widely variable across regions and that diversity estimates in contaminated sites are unremarkable compared to those in uncontaminated areas. Furthermore, the relative frequencies of haplotypes have remained statistically identical throughout multiple sampling periods. Thus, the genetic data from bank vole populations in Ukraine fail to support the hypothesis that mutational changes in contaminated regions are the product of exposure to Chernobyl radiation. Our results suggest that genetic diversity in radioactive regions of Ukraine is probably a function of natural geographic variation rather than increased mutational pressure from radiation exposure and underscore the importance of adequate geographic sampling in studies designed to elucidate the effects of toxicant exposure.
Urban-X: Towards distributed channel assignment in cognitive multi-radio mesh networks

Researches about multi-radio mesh networks have mostly focused on channel allocation under internal interference. However, the deployment of WMNs in unlicensed bands of dense urban areas imposes many challenges regarding co-existence with residential access points. In this paper, we propose Urban-X, which is a first attempt towards a new architecture for MultiRadio Cognitive Mesh Networks. We develop a novel channel assignment that reflects channel and residential traffic state of external users to maximize network throughput. We evaluate our approach using an enhancement of the ns-2 simulator. Urban-X demonstrate the feasibility of our approach and show robustness to variation of channel environment and external user traffic.
CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects

It is suggested that striatal cAMP responsive element binding protein (CREB) regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R) neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter. Compared to wild-type, drug-naïve mutants showed moderate alterations in gene expression, especially a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2. The behavioral responses to cocaine were elevated in mutant mice. Locomotor activity after acute treatment, psychomotor sensitization after intermittent drug injections and the conditioned locomotion after saline treatment were increased compared to wild-type littermates. Transgenic mice had significantly higher cocaine conditioned place preference, displayed normal extinction of the conditioned preference, but showed an augmented cocaine-seeking response following priming-induced reinstatement. This enhanced cocaine-seeking response was associated with increased levels of activity-regulated transcripts and prodynorphin. The primary reinforcing effects of cocaine were not altered in the mutant mice as they did not differ from wild-type in cocaine self-administration under a fixed ratio schedule at the training dose. Collectively, our data indicate that expression of a dominant-negative CREB variant exclusively in neurons expressing D1R is sufficient to recapitulate the previously reported behavioral phenotypes associated with virally expressed dominant-negative CREB.
A Comparison of Peak Callers Used for DNase-Seq Data

Genome-wide profiling of open chromatin regions using DNase I and high-throughput sequencing (DNase-seq) is an increasingly popular approach for finding and studying regulatory elements. A variety of algorithms have been developed to identify regions of open chromatin from raw sequence-tag data, which has motivated us to assess and compare their performance. In this study, four published, publicly available peak calling algorithms used for DNase-seq data analysis (F-seq, Hotspot, MACS and ZINBA) are assessed at a range of signal thresholds on two published DNase-seq datasets for three cell types. The results were benchmarked against an independent dataset of regulatory regions derived from ENCODE in vivo transcription factor binding data for each particular cell type. The level of overlap between peak regions reported by each algorithm and this ENCODE-derived reference set was used to assess sensitivity and specificity of the algorithms. Our study suggests that F-seq has a slightly higher sensitivity than the next best algorithms. Hotspot and the ChIP-seq oriented method, MACS, both perform competitively when used with their default parameters. However the generic peak finder ZINBA appears to be less sensitive than the other three. We also assess accuracy of each algorithm over a range of signal thresholds. In particular, we show that the accuracy of F-Seq can be considerably improved by using a threshold setting that is different from the default value.
Primary cutaneous γδ T‐cell lymphoma following mycosis fungoides

1 Requena L, Kutzner H, Palmedo G, et al. Histiocytoid Sweet’s syndrome: a dermal infiltration of immature neutrophilic granulocytes. Arch Dermatol 2005; 141: 834–842. 2 Chow S, Pasternak S, Green P, et al. Histiocytoid neutrophilic dermatoses and panniculitides: variations on a theme. Am J Dermatopathol 2007; 29: 334–341. 3 Spencer B, Nanavati A, Greene J, Butler DF. Dapsoneresponsive histiocytoid Sweet’s syndrome associated with Crohn’s disease. J Am Acad Dermatol 2008; 59: S58– S60. 4 Wu AJ, Rodgers T, Fullen DR. Drug-associated histiocytoid Sweet’s syndrome: a true neutrophilic maturation arrest variant. J Cutan Pathol 2008; 35: 220–224. 5 Murase JE, Wu JJ, Theate I, et al. Bortezomib-induced histiocytoid Sweet syndrome. J Am Acad Dermatol 2009; 60: 496–497. 6 Liu CI, Hsiao CH, Wu JT, Tsai TF. Sweet syndrome with histiocytoid infiltrate and neutropenia: a rare combination. J Am Acad Dermatol 2009; 61: 882–884.
Phenylalanine 4-monooxygenase and the role of endobiotic metabolism enzymes in xenobiotic biotransformation

Phenylalanine 4-monooxygenase is the key enzyme in the sulfoxidation of the thioether drug S-carboxymethyl-l-cysteine and its thioether metabolites, S-methyl-l-cysteine, N-acetyl-S-carboxymethyl-l-cysteine and N-acetyl-S-methyl-l-cysteine in humans, and a number of other mammalian species. The kinetics constants of the sulfoxidation reaction (Km, Vmax and CLE) have been investigated in cytosolic fractions derived from rat and human liver, in cytosolic fractions of HepG2 cells and using both human and mouse cDNA expressed phenylalanine 4-monooxygenase. Differences in Km, Vmax and CLE of S-carboxymethyl-l-cysteine have been seen in HepG2 cells and human and mouse cDNA expressed phenylalanine 4-monooxygenase when compared to both rat and human hepatic cytosolic fractions. The association of the genetic polymorphism in the sulfoxidation of S-carboxymethyl-l-cysteine is highlighted with particular reference to this biotransformation reaction as being a biomarker of disease susceptibility in Parkinson's, Alzheimer's and motor neurone diseases and in rheumatoid arthritis. The possible underlying molecular genetics of the sulfoxidation polymorphism is also discussed in relation to the known allelic frequencies of phenylalanine 4-monooxygenase. Finally, the new found role phenylalanine 4-monooxygenase plays in xenobiotic metabolism is discussed.
Solution conformation of an intramolecular DNA triplex containing a nonnucleotide linker: comparison with the DNA duplex.

The solution properties of the parallel intramolecular DNA triplex d(GAGAGA-oct-TCTCTC-oct-CTCTCT) (oct = -O-(CH2)8-O-PO2-O-(CH2)8-O-PO2-) and the duplex d(GAGAGA-oct-TCTCTC) have been examined by UV melting and high-resolution nuclear magnetic resonance spectroscopy (NMR). All nucleotides were primarily in the S conformation (i.e. near C2'-endo) in both the duplex and the triplex. However, the sugars of the Hoogsteen pyrimidine strand had a lower fraction of the S state than the Watson-Crick strands. Glycosidic torsion angles derived from nuclear Overhauser effect (NOE) build-up curves were found in the range -103 degrees to -133 degrees, with a clear alternation in magnitude along the GAGAGA strand in the triplex, whereas the glycosidic torsion angles were more similar in the duplex. Internucleotide NOEs were also consistent with an overall B-like geometry, rather than the A family. However, particularly in the Hoogsteen strand, some sequential NOE intensities were intermediate between those of the B and A forms. Distance and torsion constraints derived from NMR experiments were used to generate structures and were refined by restrained molecular dynamics. Extensive chemical shift differences between residues in the triplex and duplex were found for the purine strand, and there were remarkable differences in the pattern of shift differences for the A and G residues that correlated with differences in glycosidic torsion angles. Although there are differences in structure between the free duplex and that in the triplex, they are in important respects similar, indicating that only small conformational adjustments are needed to make parallel triple helices.
Keynote presentation at the eight international congress of behavioral medicine Mainz, Germany August 25–28, 2004

This article provides a selected overview of 20 years of research on the role of psychosocial factors in susceptibility to upper respiratory infections. We present evidence from our laboratory that psychological stress is associated with increased risk for developing respiratory illness for persons intentionally exposed to a common cold virus, that the longer the duration of the stressor the greater the risk, and that stress association with susceptibility may be mediated by stress-induced disruption of the regulation of proinflammatory cytokines. We further provide evidence that social relationships (social integration and social support) are also associated with risk for respiratory illness: Social integration is associated with reduced risk irrespective of stress level and social support protects persons from the pathogenic influences of stress. Finally, we report recent evidence that lower levels of early childhood socio-economic status (SES) are associated with greater risk of viral-induced illness during adulthood, independent of adult SES.
The Varicella-Autoantibody Syndrome

This cross-sectional study was conducted to determine the incidence of autoantibodies to phospholipids and coagulation proteins in children with acute varicella zoster virus (VZV) infection. Study groups included children with VZV alone or complicated by purpura fulminans and/or thromboembolism. VZV naïve children and children who had VZV >1 y before sample collection formed a control group. Blood was assayed for the following: free protein S (PS), protein C, antithrombin, and prothrombin; antibody binding to these proteins; lupus anticoagulant; anticardiolipin antibody; antiphospholipid antibodies; and prothrombin fragment 1+2. Data regarding coinfections was collected. Forty-three VZV-infected children showed an increased frequency of lupus anticoagulant, anticardiolipin antibody, antiphospholipid antibodies, and autoantibodies to PS, protein C, prothrombin, and antithrombin in comparison to 52 children without acute VZV (p < 0.0001). Seventeen children with VZV and purpura fulminans and/or thromboembolism showed a statistically significant decrease in free PS, significantly increased PS IgG antibody, and significantly increased prothrombin fragment 1+2 (p < 0.0001) compared with the group without acute VZV and the group with uncomplicated VZV. Twenty-six children with uncomplicated VZV showed increased PS IgG antibody (p < 0.001) compared with the children without acute VZV. For all groups combined, elevated PS IgG antibody showed negative correlation with free PS (p < 0.0001) and positive correlation with prothrombin fragment 1+2 (p = 0.0002). Autoantibodies were transient. Transient antiphospholipid and coagulation protein autoantibodies were common with VZV infection, but were not predictive of thrombotic complications.