gebhart/patrepeval huggingface dataset:
Surprising lability of biotin-streptavidin bond during transcription of biotinylated DNA bound to paramagnetic streptavidin beads. (1993)

We investigated the use of immobilized DNA templates as substrates for bacteriophage RNA polymerases in order to develop a simple method for separating template DNA from synthesized RNA. Double-stranded DNA molecules with a T7 or T3 RNA polymerase promoter at one end and a single biotin moiety at the other end were attached to streptavidin-coated paramagnetic beads and used in transcription reactions. When the biotin was attached by a nucleotide base on the nontemplate strand, the DNA-bead complex was moderately stable and could be used for multiple rounds of RNA synthesis. However, when the biotin was attached through a phosphodiester bond on the template strand, the enzymatic activity of RNA polymerase reversibly dissociated up to 80% of biotinylated DNA from the streptavidin beads. Biotinylated DNA bound to streptavidin beads in this system with a binding constant on the order of 10(12) M-1. These results stress the need for careful evaluation of solid phase adaptations of standard solution reactions in molecular biology.
Bacillus subtilis antibiotics: structures, syntheses and specific functions (2005)

The endospore-forming rhizobacterium Bacillus subtilis- the model system for Gram-positive organisms, is able to produce more than two dozen antibiotics with an amazing variety of structures. The produced anti-microbial active compounds include predominantly peptides that are either ribosomally synthesized and post-translationally modified (lantibiotics and lantibiotic-like peptides) or non-ribosomally generated, as well as a couple of non-peptidic compounds such as polyketides, an aminosugar, and a phospholipid. Here I summarize the structures of all known B. subtilis antibiotics, their biochemistry and genetic analysis of their biosyntheses. An updated summary of well-studied antibiotic regulation pathways is given. Furthermore, current findings are resumed that show roles for distinct B. subtilis antibiotics beyond the "pure" anti-microbial action: Non-ribosomally produced lipopeptides are involved in biofilm and swarming development, lantibiotics function as pheromones in quorum-sensing, and a "killing factor" effectuates programmed cell death in sister cells. A discussion of how these antibiotics may contribute to the survival of B. subtilis in its natural environment is given.
Untraceable secret credentials: trust establishment with privacy (2004)

There is generally no a priori trust relationship among entities interacting in pervasive computing environments which makes it necessary to establish trust from scratch. This task becomes extremely challenging when it is simultaneously necessary to protect the privacy of the actors involved. We show how trust can be based on previous interactions yet remain unlinkable to any previous event or any specific entity. A solution based on group blind signatures is proposed that relies on credentials both secret, meaning that they contain an encrypted description of previous interactions, and untraceable, meaning that they cannot be recognized when presented to their issuer.
Overexpression of Klotho suppresses liver cancer progression and induces cell apoptosis by negatively regulating wnt/β-catenin signaling pathway (2015)

Klotho was a tumor suppressor gene, and overexpression of Klotho suppressed the proliferation of liver cancer cells partly due to negative regulation of Wnt/β-catenin signaling pathway. So, Klotho might be used as a potential target, and the study will contribute to treatment for therapy of liver cancer patients.
Exploiting high-level descriptions for circuits fault tolerance assessments (2002)

The paper proposes a new approach to estimate early the fault detection capability of a safety-critical computer-based system from its high-level description. This paper first aims at verifying the correspondence between dependability measures obtained through simulation-based fault injection experiments at different levels of abstraction. Then, we propose Alternative Graphs (AGs) to create lists of malicious faults without expanding the full data flow, whose size can often explode. Fault trees are exploited to improve the results of the high-level fault analysis. To evaluate the effectiveness of the approach, simulation-based fault injection experiments have been done on some benchmark systems described in VHDL language. The approach demonstrates that fault detection analysis performed at a high-level is less CPU time demanding but approximates well the fault detection measures achievable on a low-level system description.
Targeting Polo-Like Kinase: Learning Too Little Too Late? (2008)

David Olmos, The Drug Development Unit, Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Surrey, United Kingdom Charles Swanton, Cancer Research UK Translational Cancer Therapeutics Laboratory, London Research Institute, London, United Kingdom Johann de Bono, The Drug Development Unit, Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Surrey, United Kingdom
Amplification of large artificial chromosomes. (1990)

Yeast artificial chromosome cloning is an attractive technology for genomic mapping studies because very large DNA segments can be readily propagated. However, detailed analyses often require the extensive application of blotting-hybridization techniques because artificial chromosomes are normally present at only one copy per haploid genome. We have developed a cloning vector and host strain that alleviate this problem by permitting copy number amplification of artificial chromosomes. The vector includes a conditional centromere that can be turned on or off by changing the carbon source. Strong selective pressure for extra copies of the artificial chromosome can be applied by selecting for the expression of a heterologous thymidine kinase gene. When this system was used, artificial chromosomes ranging from about 100 to 600 kilobases in size were readily amplified 10- to 20-fold. The selective conditions did not induce obvious rearrangements in any of the clones tested. Reactivation of the centromere in amplified artificial chromosome clones resulted in stable maintenance of an elevated copy number for 20 generations. Applications of copy number control to various aspects of artificial chromosome analysis are addressed.
Acute Myelogenous Leukaemia (2010)

Abstract Acute myelogenous leukaemia is the result of a malignant transformation of a single primitive multipotential marrow haematopoietic cell, converting it to a leukaemic stem cell. This neoplastic transformation imparts a growth and survival advantage to the cell clone that emerges. Leukaemic cells fill the haematopoietic cords of marrow. The functional result of this alteration is to impair normal blood cell production in the marrow, leading to a profound decrease in normal red cells (anaemia), white cells (leucopaenia) and platelets or thrombocytes (thrombocytopaenia) in the blood. The disease is rapidly progressive, unless treated promptly. Therapy usually consists of at least two drugs, cytosine arabinoside and an anthracycline antibiotic (e.g. daunomycin). The response of the disease to treatment is dependent on several factors but the two most compelling are the age at diagnosis and the cytogenetic and genetic features of the cells with older age and unfavourable chromosomal karyotypes decreasing the proportion of long‐term remissions. Key Concepts: Cancer of any type is the result of a series of gene mutations in a single tissue cell. Acute myelogenous leukaemia, like all cancers, originates in a single tissue cell, in this case within haematopoietic tissue. The incidence of acute myelogenous leukaemia can be increased by the inheritance of predisposition genes that are unapparent (nonsyndromic familial cases) or apparent as manifest by syndromic cases, such as Fanconi anaemia. Leukaemic cells accumulate because they have a proliferative and survival advantage compared to normal cells. It is estimated that approximately one trillion leukaemic cells are present at diagnosis. Very small proportions of these cells are leukaemic stem cells, which sustain leukaemic haematopoiesis. Acute myelogenous leukaemia stem cells have multipotential haematopoietic lineage potential. Thus, they can differentiate into leukaemic precursor cells of all haematopoietic lineages. The predominance of one or two leads to the phenotypic classification of acute myelogenous leukaemia (e.g. erythroid, monocytic, megakaryocytic and myelomonocytic). The accumulation of leukaemic cells in the marrow secondarily suppresses normal blood cell development. Chemotherapy is predicated on the coexistence of normal haematopoietic stem cells and leukaemic stem cells in the marrow. Suppression of leukaemic cell accumulation by at least three logs by chemotherapy can, in many cases, result in the release of inhibition of normal stem cells and a return of normal haematopoiesis for a variable time.
Association of Increasing Burn Severity in Mice With Delayed Mobilization of Circulating Angiogenic Cells (2010)

If CAC mobilization and wound perfusion are important determinants of clinical outcome, then strategies designed to augment angiogenic responses may improve outcome in patients with severe burn wounds.
Processing procedures and feeding systems for sorghum-based diets given to lactating sows (1994)

One-hundred twenty nine primiparous sows were used to determine the effects of alternative processing procedures and feeding systems on the nutritional value of sorghum grain-based diets for lactating sows. Treatments were a ground sorghum control, steam- flaked sorghum and extruded sorghum fed in meal form, or the ground sorghum control given as pellets or gruel (1: 1 ratio of water and feed on a volume:volume basis). Average daily feed intake was greater for sows fed pelleted and gruel forms compared to sow fed the diets with steam-flaked and extruded sorghum. However, no differences occurred in sow weight or backfat losses among the treatments. Number of pigs weaned and percentage survivability were similar among treatments, except that steam-flaked sorghum supported greater litter weight gains than extruded sorghum. Apparent digestibilities of OM, N, and GE in sows fed steam-flaked and extruded sorghum were greater than in sows fed pelleted or gruel diets. Sows fed extruded sorghum tended to have the greatest digestibilities of OM, N, and GE and lowest excretions of DM and N in the feces. Severity of ulceration was not affected significantly by treatments, but keratinization was greatest for sows fed extruded sorghum. In conclusion, the alternative processing methods (steam-flaking and extrusion) and feeding systems (pellets and gruel) had little effect on sow and liner performance. However, nutrient digestibilities were improved for all treatments that involved heating (steam flaking, extrusion, and pelleting), and, thus, these treatments resulted in less fecal excretion of DM and N.; Swine Day, Manhattan, KS, November 17, 1994
Structure–Activity Relationships of Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Investigations of Various 6,5-Heterocycles to Improve Metabolic Stability (2011)

N-(6-(6-Chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (1) is a potent and efficacious inhibitor of PI3Kα and mTOR in vitro and in vivo. However, in hepatocyte and in vivo metabolism studies, 1 was found to undergo deacetylation on the 2-amino substituent of the benzothiazole. As an approach to reduce or eliminate this metabolic deacetylation, a variety of 6,5-heterocyclic analogues were examined as an alternative to the benzothiazole ring. Imidazopyridazine 10 was found to have similar in vitro potency and in vivo efficacy relative to 1, while only minimal amounts of the corresponding deacetylated metabolite of 10 were observed in hepatocytes.
Molecular Basis of Evolutionary Loss of the α1,3-Galactosyltransferase Gene in Higher Primates (2002)

Galactose-alpha1,3-galactose (alphaGal) epitopes, the synthesis of which requires the enzyme product of alpha1,3-galactosyltransferase (alpha1,3GT), are sugar chains on the cell surface of most mammalian species. Notable exceptions are higher primates including Old World monkeys, apes, and humans. The alphaGal-negative species as well as mice with deletion of the alpha1,3GT gene produce abundant anti-alphaGal antibodies. The evolutionary loss of alphaGal epitopes has been attributed to point mutations in the coding region of the gene. Because no transcripts could be found in the higher primate species with Northern blot analysis, a potential alternative explanation has been loss of upstream regulation of the gene. Here, we have demonstrated that the rhesus promoter is functional. More importantly, a variety of full-length transcripts were detected with sensitive PCR-based methods in the tissues of rhesus monkeys, orangutans, and humans. Five crucial mutations were delineated in the coding region of the human and rhesus and three in the orangutan, any one of which could be responsible for inactivation of the alpha1,3GT gene. Two of the mutations were shared by all three higher primates. These findings, which elucidate the molecular basis for the evolutionary loss of alphaGal expression, may have implications in medical research.
The FoldX web server: an online force field (2005)

FoldX is an empirical force field that was developed for the rapid evaluation of the effect of mutations on the stability, folding and dynamics of proteins and nucleic acids. The core functionality of FoldX, namely the calculation of the free energy of a macromolecule based on its high-resolution 3D structure, is now publicly available through a web server at http://foldx.embl.de/. The current release allows the calculation of the stability of a protein, calculation of the positions of the protons and the prediction of water bridges, prediction of metal binding sites and the analysis of the free energy of complex formation. Alanine scanning, the systematic truncation of side chains to alanine, is also included. In addition, some reporting functions have been added, and it is now possible to print both the atomic interaction networks that constitute the protein, print the structural and energetic details of the interactions per atom or per residue, as well as generate a general quality report of the pdb structure. This core functionality will be further extended as more FoldX applications are developed.
Compatibility is not transparency: VMM detection myths and realities (2007)

Hypokalemic can increase transmural heterogeneity of C×43 expression and repolarization in left ventricular myocardium of rabbit, and decrease VFT and can induce MVA more easily.
Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments (2010)

Several conditions in clinical orthopaedic practice can lead to the development of a diaphyseal segmental bone defect, which cannot heal without intervention. Segmental bone defects have been traditionally treated with bone grafting and/or distraction osteogenesis, methods that have many advantages, but also major drawbacks, such as limited availability, risk of disease transmission and prolonged treatment. In order to overcome such limitations, biological treatments have been developed based on specific pathways of bone physiology and healing. Bone tissue engineering is a dynamic field of research, combining osteogenic cells, osteoinductive factors, such as bone morphogenetic proteins, and scaffolds with osteoconductive and osteoinductive attributes, to produce constructs that could be used as bone graft substitutes for the treatment of segmental bone defects. Scaffolds are usually made of ceramic or polymeric biomaterials, or combinations of both in composite materials. The purpose of the present review is to discuss in detail the molecular and cellular basis for the development of bone tissue engineering constructs.
Layered coding using bitstream decomposition with drift correction (1997)

It is well known that layered video coding is useful both for service interworking and as an aid to error resilience. A major drawback of layered coding is that it invariably results in a reduction in overall coding efficiency for the high quality service. An attractive approach would be one in which the high quality service is coded, and then the resulting bitstream is decomposed in such a way that the lower resolution services can be reconstructed using only a subset of the total generated data. This would mean that there would be no impact on the coding efficiency of the highest quality service. In this paper we demonstrate that the quality of the lower layer when this approach is used is fundamentally limited by drift. It is shown that even a coarsely quantized, low rate correction signal provides a major benefit to the quality of this lower layer service while still not impacting significantly on the coding efficiency of the high quality service. Of course, some overhead is introduced in the coding of the lower quality service but the total overhead is still significantly better than simulcast.
Specific Antagonism of PDGF Prevents Renal Scarring in Experimental Glomerulonephritis (2001)

Glomerular mesangial cell proliferation and/or mesangial matrix accumulation characterizes many progressive renal diseases. Rats with progressive mesangioproliferative glomerulonephritis were treated from day 3 to day 7 after disease induction with a high-affinity oligonucleotide aptamer antagonist against platelet-derived growth factor-B chain (PDGF-B). In comparison with nephritic rats that received vehicle or a scrambled aptamer, treatment with the PDGF-B aptamer led to a significant reduction of mesangioproliferative changes, glomerular hypertrophy, podocyte damage, and glomerular macrophage influx on day 8. Both nephritic control groups subsequently developed progressive proteinuria and decreased renal function. On day 100, glomerulosclerosis, tubulointerstitial damage, glomerular and interstitial accumulation of types III and IV collagen, and overexpression of transforming growth factor-beta were widespread. All of these chronic changes were prevented in rats that received the PDGF-B aptamer, and their functional and morphologic parameters on day 100 were largely indistinguishable from non-nephritic rats. These data provide the first evidence for a causal role of PDGF in the pathogenesis of renal scarring and point to a new, highly effective therapeutic approach to progressive, in particular mesangioproliferative, renal disease.
Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease (2004)

Degeneration of the nigrostriatal dopaminergic pathway, the hallmark of Parkinson's disease, can be recapitulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. Herein, we demonstrate that adoptive transfer of copolymer-1 immune cells to MPTP recipient mice leads to T cell accumulation within the substantia nigra pars compacta, suppression of microglial activation, and increased local expression of astrocyte-associated glial cell line-derived neurotrophic factor. This immunization strategy resulted in significant protection of nigrostriatal neurons against MPTP-induced neurodegeneration that was abrogated by depletion of donor T cells. Such vaccine treatment strategies may provide benefit for Parkinson's disease.
Identification of O‐linked oligosaccharide chains in the activation peptides of blood coagulation factor X (1993)

Conversion of factor X to factor Xa results in release of a heavily glycosylated activation peptide. Analysis of protease-digested glycopeptides derived from the activation peptides of bovine and human blood coagulation factor X allowed the identification of sites of the O-linked oligosaccharide chains in these peptides. Glycopeptides were prepared from the activation peptides by digestion with chymotrypsin or Staphylococcus aureus V8 protease. By combined analysis of amino acid sequence and sialic acid content, we found that bovine factor X had an O-linked oligosaccharide chain linked to Thr26, and human factor X had four carbohydrate-attachment sites, namely, O-glycosidic linkages to Thr17 and Thr29, respectively, and N-glycosidic linkages to Asn39 and Asn49, respectively, in their activation peptides. The O-linked carbohydrate-attachment sites were identified since the yields of phenylthiohydantoin derivatives of amino acids that corresponded to their residues were increased during amino acid sequencing after deglycosylation of the glycopeptides with sialidase and O-glycanase. The effect of deglycosylation of bovine factor X1 was investigated with factor-X-activating enzyme from Russell's viper venom or extrinsic Xase (factor VIIa/tissue factor/phospholipid) by examining the activation rates of derivatives of factor X prepared using O-glycanase, sialidase, and/or N-glycanase. The removal of O-linked carbohydrate resulted in a decrease in the rate of activation. It appears that carbohydrate residues in factor X play an important role in the activation of the zymogen.
Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study (2017)

CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble <i>α</i>-klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m<sup>2</sup> and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism.
Testing embedded-core-based system chips (1999)

Recently, designers have been embedding reusable modules to build on-chip systems that form rich libraries of predesigned, preverified building blocks. These embedded cores make it easier to import technology to a new system and differentiate the corresponding product by leveraging intellectual property advantages. Most importantly, design reuse shortens the time-to-market for new systems. The attributes that make system chips built with embedded IP cores an attractive methodology-design reuse, heterogeneity, reconfigurability, and customizability-also make testing and debugging these chips a complex challenge. The authors review the various alternatives for testing embedded cores and describe solutions and proposed standards that are expected to play a key role in developing the core based design paradigm.