gebhart/patrepeval huggingface dataset:
Different conformational forms of Escherichia coli and rat liver 5S rRNA revealed by Pb(II)‐induced hydrolysis (1992)

Different stable forms of Escherichia coli and rat liver 5S rRNA have been probed by Pb(II)-induced hydrolysis. In the native A forms of 5S rRNA, Pb2+ reveal single-stranded RNA stretches and regions of increased conformational flexibility or distorted by the presence of bulged nucleotides. Hydrolysis of urea/EDTA-treated E. coli 5S rRNA (B form) shows the presence of two strong helical domains; helix A retained from the A form and a helix composed of RNA regions G33-C42 and G79-C88. Other RNA regions resistant to hydrolysis may be involved in alternative base pairing, causing conformational heterogeneity of that form. Pb(II)-induced hydrolysis distinguishes two different forms of rat liver 5S rRNA; the native A form and the form obtained by renaturation of 5S rRNA in the presence of EDTA. Pb(II)-hydrolysis data suggest that both forms are highly structured. In the latter form, the orientation of the bulged C66 is changed with respect to helix B. At the same time, a new helical segment is possibly formed, composed of nucleotides from helix C and loop c on one side and from helix E and loop d' on the other.
Inflammation-related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function (2010)

Together with an inflammatory reaction, influenza A vaccine induced platelet activation and sympathovagal imbalance towards adrenergic predominance. Significant correlations were found between CRP levels and HRV parameters, suggesting a pathophysiological link between inflammation and cardiac autonomic regulation. The vaccine-related platelet activation and cardiac autonomic dysfunction may transiently increase the risk of cardiovascular events.
The Polycomb protein shares a homologous domain with a heterochromatin-associated protein of Drosophila. (1991)

The Polycomb (Pc) gene of Drosophila melanogaster is a member of a large class of genes (Pc group) required for the segment-specific repression of homeotic selector genes. Mutations in Pc-group genes show strong posterior transformations in homozygous embryos resulting from an ectopic expression of homeotic genes in segments where they are not supposed to be active. Genetic evidence suggests that Pc is part of a cellular memory mechanism responsible for the transmission of the homeotic expression pattern through developmental time. We have determined the nucleotide sequence for the genomic DNA of the Pc gene and for cDNAs corresponding to the 2.5-kilobase Pc mRNA. The deduced sequence of the Pc protein exhibits a homology to the heterochromatin-associated protein HP1 encoded by the suppressor of position effect variegation gene Su(var) 205. The homology is confined to a 37-amino acid domain in the N-terminal part of the two proteins. Our findings extend to the molecule level the genetically identified parallels between the Pc-group genes and the modifiers of position effect variegation. This suggests that Pc could use analogous mechanisms at the level of the higher order chromatin structure for the stable transmission of a determined state, as has been proposed for the clonal propagation of heterochromatin domains.
The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects (2000)

The findings are further evidence that the 17 U+17X/137X urinary ratio is not a robust measure of CYP1A2 activity. A possible mechanism by which the ratio might be influenced by NAT2 genotype is suggested.
Trace Metal-Citric Acid Complexes as Inhibitors of Calcification and Crystal Formation (1982)

At high citrate:metal ratios the small polyvalent metals Fe3+, Be2+, Al3+, and Cr3+ interact with citrate to form potent inhibitors of both calcium uptake by a calcifiable matrix and crystal formation from a metastable solution of calcium phosphate. These unique metal-citrate complexes are effective inhibitors at 0.2-30 × 10−6M, with iron (III) citrate being the most potent. The inhibitor effects of mixtures of the metal-citrate complexes are additive. These observations define a new role for citrate and indicate how certain trace elements may, by interaction with citrate, be important determinants in the control of calcium salt deposition in vivo. The possible pertinence of these observations to the deposition of calcium salts within the kidney and to the prevalence of idiopathic calculi in various geographic areas is now under investigation.
Periostin is expressed within the developing teeth at the sites of epithelial–mesenchymal interaction (2004)

Periostin was originally isolated as an osteoblast-specific factor that functions as a cell adhesion molecule for preosteoblasts and is thought to be involved in osteoblast recruitment, attachment, and spreading. The protein was renamed "periostin" because of its expression in the periosteum and periodontal ligament, indicating a potential role in bone and maintenance of tooth structure. Periostin has structural similarity to insect fasciclin-I and can be induced by TGF-beta and Bmp2. Because tooth and periodontium development is a well-described genetic model for organogenesis governed by a reciprocal set of epithelial-mesenchymal interactions, thought to be controlled by various TGF-beta superfamily members, we investigated whether periostin is present during tooth morphogenesis. Both periostin mRNA and protein expression were analyzed throughout normal tooth development (embryonic day [E] 9.5-newborn) and within both Bmp4- and Msx2-null embryos. Periostin mRNA is initially present within the E9.5 first branchial arch epithelium and then shifts to underlying ectomesenchyme. Both mRNA and protein are asymmetrically localized to the lingual/palatal and buccal side during the early epithelial-mesenchymal interactions. Periostin is also present in dental papilla cells and within the trans-differentiating odontoblasts during the bell and hard tissue formation stages of tooth development. We suggest that periostin plays multiple roles as a primary responder molecule during tooth development and may be linked to deposition and organization of other extracellular matrix adhesion molecules during maintenance of the adult tooth, particularly at the sites of hard-soft tissue interface.
Modulation of Cellular Thermoresistance and Actin Filament Stability Accompanies Phosphorylation-Induced Changes in the Oligomeric Structure of Heat Shock Protein 27 (1995)

Phosphorylation of heat shock protein 27 (HSP27) can modulate actin filament dynamics in response to growth factors. During heat shock, HSP27 is phosphorylated at the same sites and by the same protein kinase as during mitogenic stimulation. This suggests that the same function of the protein may be activated during growth factor stimulation and the stress response. To determine the role of HSP27 phosphorylation in the heat shock response, several stable Chinese hamster cell lines that constitutively express various levels of the wild-type HSP27 (HU27 cells) or a nonphosphorylatable form of human HSP27 (HU27pm3 cells) were developed. In contrast to HU27 cells, which showed increased survival after heat shock, HU27pm3 cells showed only slightly enhanced survival. Evidence is presented that stabilization of microfilaments is a major target of the protective function of HSP27. In the HU27pm3 cells, the microfilaments were thermosensitized compared with those in the control cells, whereas wild-type HSP27 caused an increased stability of these structures in HU27 cells. HU27 but not HU27pm3 cells were highly resistant to cytochalasin D treatment compared with control cells. Moreover, in cells treated with cytochalasin D, wild-type HSP27 but not the phosphorylated form of HSP27 accelerated the reappearance of actin filaments. The mutations in human HSP27 had no effect on heat shock-induced change in solubility and cellular localization of the protein, indicating that phosphorylation was not involved in these processes. However, induction of HSP27 phosphorylation by stressing agents or mitogens caused a reduction in the multimeric size of the wild-type protein, an effect which was not observed with the mutant protein. We propose that early during stress, phosphorylation-induced conformational changes in the HSP27 oligomers regulate the activity of the protein at the level of microfilament dynamics, resulting in both enhanced stability and accelerated recovery of the filaments. The level of protection provided by HSP27 during heat shock may thus represent the contribution of better maintenance of actin filament integrity to overall cell survival.
Blockade of CD28 During In Vitro Activation of Encephalitogenic T Cells or After Disease Onset Ameliorates Experimental Autoimmune Encephalomyelitis (1999)

Previous studies have shown complex roles for the B7 receptors in providing both positive and negative regulation of experimental autoimmune encephalomyelitis (EAE). B7 blockade can ameliorate clinical EAE by indirectly interfering with CD28 signaling. However, B7 blockade can also result in disease exacerbation, presumably by interfering with regulatory B7:CTLA-4 interactions. Therefore, we have directly targeted T cell CD28 with specific mAbs both during initial Ag priming and after the onset of clinical signs of EAE. We found that CD28 blockade ameliorated EAE during the efferent and afferent limbs of the immune response. Disease amelioration at disease onset was associated with suppression of TNF-alpha production. Finally, Ab blockade of T cell CD28 during the first disease episode resulted in significant attenuation of the subsequent disease course, with no significant relapses. In contrast to previous studies targeting APC B7 with CTLA4-Ig, reagents targeting CD28 can block ongoing disease. Therefore, the present results suggest a clinically relevant therapeutic scenario for human diseases, such as multiple sclerosis.
The Current Status of PARP Inhibitors in Ovarian Cancer (2016)

Recent advances in our understanding of the molecular biology of epithelial ovarian cancer have led to the development of a number of targeted therapies, including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. It has become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this therapeutic approach. Importantly, companion homologous recombination deficiency scores are being developed to help guide the selection of patients most likely to gain clinical benefit from PARP inhibition. Olaparib, the first and most extensively investigated PARP inhibitor, is now licensed in Europe for maintenance treatment of patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high-grade serous ovarian cancer who have responded to platinum-based chemotherapy. In the United States, olaparib is licensed for treatment of patients with germline BRCA-mutated ovarian cancer who have received 3 or more lines of chemotherapy. There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. This review will focus on the current evidence for PARP inhibitors in ovarian cancer and discuss ongoing clinical trials and future research directions in this rapidly evolving area.
Atherosclerosis, Dyslipidemia, and Inflammation: The Significant Role of Polyunsaturated Fatty Acids (2013)

Phospholipids play an essential role in cell membrane structure and function. The length and number of double bonds of fatty acids in membrane phospholipids are main determinants of fluidity, transport systems, activity of membrane-bound enzymes, and susceptibility to lipid peroxidation. The fatty acid profile of serum lipids, especially the phospholipids, reflects the fatty acid composition of cell membranes. Moreover, long-chain n-3 polyunsatured fatty acids decrease very-low-density lipoprotein assembly and secretion reducing triacylglycerol production. N-6 and n-3 polyunsatured fatty acids are the precursors of signalling molecules, termed "eicosanoids," which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 polyunsatured fatty acids have proinflammatory actions, while eicosanoids derived from n-3 polyunsatured fatty acids have anti-inflammatory ones. Previous studies showed that inflammation contributes to both the onset and progression of atherosclerosis: actually, atherosclerosis is predominantly a chronic low-grade inflammatory disease of the vessel wall. Several studies suggested the relationship between long-chain n-3 polyunsaturated fatty acids and inflammation, showing that fatty acids may decrease endothelial activation and affect eicosanoid metabolism.
Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics (2012)

Selected reaction monitoring on a triple quadrupole mass spectrometer is currently experiencing a renaissance within the proteomics community for its, as yet, unparalleled ability to characterize and quantify a set of proteins reproducibly, completely, and with high sensitivity. Given the immense benefit that high resolution and accurate mass instruments have brought to the discovery proteomics field, we wondered if highly accurate mass measurement capabilities could be leveraged to provide benefits in the targeted proteomics domain as well. Here, we propose a new targeted proteomics paradigm centered on the use of next generation, quadrupole-equipped high resolution and accurate mass instruments: parallel reaction monitoring (PRM). In PRM, the third quadrupole of a triple quadrupole is substituted with a high resolution and accurate mass mass analyzer to permit the parallel detection of all target product ions in one, concerted high resolution mass analysis. We detail the analytical performance of the PRM method, using a quadrupole-equipped bench-top Orbitrap MS, and draw a performance comparison to selected reaction monitoring in terms of run-to-run reproducibility, dynamic range, and measurement accuracy. In addition to requiring minimal upfront method development and facilitating automated data analysis, PRM yielded quantitative data over a wider dynamic range than selected reaction monitoring in the presence of a yeast background matrix because of PRM's high selectivity in the mass-to-charge domain. With achievable linearity over the quantifiable dynamic range found to be statistically equal between the two methods, our investigation suggests that PRM will be a promising new addition to the quantitative proteomics toolbox.
Optical Coherence Tomography (2000)

Abstract Optical coherence tomography (OCT) is a technique with which to peer inside a body noninvasively. Tissue structure defined by tissue absorption and scattering coefficients, and the speed of blood flow, are derived from the characteristics of light remitted by the body. Singly backscattered light detected by partial coherence interferometry (PCI) is used to synthesize the tomographic image coded in false colors. A prerequisite of this technique is a low time‐coherent but high space‐coherent light source, usually a superluminescent diode or a multimode semiconductor laser. This limits the wavelengths to the red and near‐infrared (NIR) region from about 600 nm to 1300 nm, the so‐called therapeutic window, where absorption (μ a ≈ 0.01 mm −1 ) is small enough. Transverse resolution in OCT is diffraction limited, as in conventional imaging; depth resolution is limited by the coherence length of the light. Both figures are of the order of micrometers. Velocity resolution is of the order of 0.1 mm s −1 . A few instruments are commercially available. At present, OCT is mainly used in the medical field, in particular in ophthalmology. Owing to the high transmissivity of ocular media, the depth penetration is considerable. Corresponding applications in dermatology are somewhat hindered by the strong scattering of epidermic tissue (μ s ≈ 10 2 mm −1 ). As OCT provides images with a resolution comparable to conventional histology, but in real time, it can be used as a biopsy technique in a wide range of biological systems to detect diseases. These include the tomographic imaging of the internal microstructure of in vitro atherosclerotic plaques, the tomographic real‐time diagnostics for intraoperative monitoring, and in microsurgical intervention. Optical biopsy based on OCT also provides diagnostic information by differentiating the architectural morphology of urological tissue, gastrointestinal tissue, and respiratory tissue.
Chronic Infections and Atherosclerosis (2007)

Immunoinflammatory processes due to chronic infection are thought to be one of the definitive atherogenetic processes. Especially, anti-heat shock protein antibodies have been related to the prevalence of disease such as coronary artery disease or cerebral infarction, etc., resulted from atherosclerosis. Furthermore, the presence of HSP60-specific T lymphocytes in circulation may increase the risk of atherosclerosis. We have recently demonstrated the evidences that Helicobacter pylori infection induced atherosclerosis in apoe+/- ldlr+/- mice and that Hp-anti-heat-shock protein specific Th1-dominant immune responses had a major involvement in the progression of atherosclerosis. These cellular immune responses caused autoimmunity against endogenous HSP60 (expressed on the stressed cells of vascular endothelium), due to the molecular mimicry. Therefore, an appropriate treatment with antibiotics or with anti-HSP60 antibodies, which regulates the Th1 induction, could sufficiently reduce the progression of atherosclerosis.
An update on lipotoxic endoplasmic reticulum stress in pancreatic β-cells (2008)

The UPR (unfolded protein response) or ER (endoplasmic reticulum) stress response was first described 20 years ago. The field of ER stress has expanded tremendously since, moving from basic biology in yeast to human neurodegenerative, inflammatory, cardiovascular and neoplastic diseases. The ER stress response has also been implicated in diabetes development, affecting both insulin production by pancreatic beta-cells and insulin sensitivity in peripheral tissues. In the present mini-review, we focus on recent progress in the field of ER stress in pancreatic beta-cells. Recent advances in the understanding of lipotoxic ER stress and beta-cell recovery from ER stress are discussed.
Dietary lipids from an evolutionary perspective: sources, structures and functions (2011)

Lipids are a complex group of biomolecules whose precise functions remain poorly understood. As a result of this poor understanding, it is difficult to make mechanistically based recommendations for appropriate dietary intakes. It is equally difficult to develop methods that are capable of diagnosing functional impairments because of insufficiencies or excesses in particular fatty acids. Lipids are abundant building blocks of cellular membranes, supply components for lipid particle assembly and substrates for metabolic fuel, and provide a precursor pool for an astonishingly diverse range of signalling molecules. In each of these broad functions, the functional consequences of different structures of fatty acids are not fully understood. According to research on membrane functions through early evolution, docosahexaenoic acid provides two biophysical properties to membranes - accelerating the lateral motion of lipids and proteins within the plane of the membrane and simultaneously slowing the rate of diffusion/leakage of charged species across the plane of the membrane. The range of fatty acid structures used as substrates for assembly of either lipoproteins or milk fat globules is broad, yet the functional consequences of differences are not known. Different lipids signal into a remarkable range of biological processes. Saturated and monounsaturated fatty acids are becoming recognized as signal molecules in their own right. The complex composition of human milk lipids implies that diets with a diversity of fatty acids in complex lipid forms and structures is more beneficial than a narrow range of any particular group of fatty acids.
Pooled Human IgG Hyperimmune for Type III Group B Streptococci: Evaluation against Multiple Strains In Vitro and in Experimental Disease (1991)

Because rates of morbidity and mortality due to newborn sepsis are unacceptably high, adjunctive therapies must be investigated. In the current studies, after healthy adults were immunized with type III group B streptococcal (III-GBS) capsular polysaccharide vaccine, serum was obtained from "vaccine-responders" from which a pooled human IgG preparation hyperimmune for III-GBS was prepared by ion-exchange column chromatography. This preparation, containing 549 micrograms/ml III-GBS antibody was very active functionally when evaluated against multiple III-GBS strains both in vitro in an opsonophagocytic assay using newborn sera and in a newborn rat model of III-GBS disease. The level of functional activity was dramatically higher than that of commercially available human IgG preparations for intravenous use demonstrated previously in identical assays. Human IgG preparations hyperimmune for GBS offer promise for use as adjunctive therapy of sepsis in newborns.
ConSurf: Identification of Functional Regions in Proteinsby Surface-Mapping of Phylogenetic Information (2002)

A set of examples is available at http://consurf.tau.ac.il under 'GALLERY'.
The Intel 80×86 processor architecture: pitfalls for secure systems (2002)

An in-depth analysis of the 80/spl times/86 processor families identifies architectural properties that may have unexpected, and undesirable, results in secure computer systems. In addition, reported implementation errors in some processor versions render them undesirable for secure systems because of potential security and reliability problems. We discuss the imbalance in scrutiny for hardware protection mechanisms relative to software, and why this imbalance is increasingly difficult to justify as hardware complexity increases. We illustrate this difficulty with examples of architectural subtleties and reported implementation errors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Performance issues of a distributed frame buffer on a multicomputer (1998)

A multiple-port, distributed frame buffer has been recently proposed to support parallel rendering on multicomputers. This paper describes an implementation of such a distributed frame buffer for the Intel Paragon routing network, and reports its performance results. We have conducted several experiments with the system we have developed. Our results indicate that placing a multipleport, distributed frame buffer directly on the host internal routing network can provide high throughput to eliminate the bottleneck of merging a final image from multiple processors to a frame buffer. This architectural approach can also effectively support image composition for sort-last. The synchronization algorithm we have developed requires only one-way communication and minimizes receive overhead for message passing to the frame buffer.