gebhart/patrepeval huggingface dataset:
Understanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors (2017)

Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA approved, while another two have shown promising activity and are in late stage development. Nonetheless, both primary and secondary resistance to PARP inhibition have led to treatment failure, and the development of predictive biomarkers and the ability to identify and overcome mechanisms of resistance is vital for optimization of its clinical utility. Additionally, there has been evidence that PARP inhibition may have a therapeutic role beyond HR deficient tumors which warrants further investigation, both as single agent and in combination with other therapeutic modalities like cytotoxic chemotherapy, radiation, targeted therapy and immunotherapy. With new strategies to overcome resistance and expand its therapeutic utility, PARP inhibitors are likely to become a staple in our armamentarium of drugs in cancer therapeutics.
The Concentration of Circulating Corticotropin-releasing Hormone mRNA in Maternal Plasma Is Increased in Preeclampsia (2003)

Plasma CRH mRNA represents a new molecular marker for preeclampsia. Maternal plasma RNA is gender- and polymorphism-independent and may allow noninvasive gene-expression profiling of an unborn fetus.
Thermodynamics of the binding of galactopyranoside derivatives to the basic lectin from winged bean (Psophocarpus tetrogonolobus). (1991)

The thermodynamics of the binding of D-galactopyranoside (Gal), 2-acetamido-2-deoxygalactopyranoside (GalNAc), methyl-alpha-D-galactopyranoside, and methyl-beta-D-galactopyranoside to the basic agglutinin from winged bean (WBAI) in 0.02 M sodium phosphate and 0.15 M sodium chloride buffer have been investigated from 298.15 to 333.15 K by titration calorimetry and at the denaturation temperature by differential scanning calorimetry (DSC). WBAI is a dimer with two binding sites. The titration calorimetry yielded single-site binding constants ranging from 0.56 +/- 0.14 x 10(3) M-1 for Gal at 323.15 K to 7.2 +/- 0.5 x 10(3) M-1 for GalNAc at 298.15 K and binding enthalpies ranging from -28.0 +/- 2.0 kJ mol-1 for GalNAc at 298.15 K to -14.3 +/- 0.1 kJ mol-1 for methyl-beta-D-galactopyranoside at 322.65 K. The denaturation transition consisted of two overlapping peaks over the pH range 5.6-7.4. Fits of the differential scanning calorimetry data to a two-state transition model showed that the low temperature transition (341.6 +/- 0.4 K at pH 7.4) consisted of two domains unfolding as a single entity while the higher temperature transition (347.8 +/- 0.6 K at pH 7.4) is of the remaining WBAI dimer unfolding into two monomers. Both transitions shift to higher temperatures and higher calorimetric enthalpies with increase in added ligand concentration at pH 7.4. Analysis of the temperature increase as a function of added ligand concentration suggests that one ligand binds to the two domains unfolding at 341.6 +/- 0.6 K and one ligand binds to the domain unfolding at 347.8 +/- 0.6 K.
Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function (1991)

Like other DNA-containing viruses, the three origins of herpes simplex virus type 1 (HSV-1) DNA replication are flanked by sequences containing transcriptional regulatory elements. In a transient plasmid replication assay, deletion of sequences comprising the transcriptional regulatory elements of ICP4 and ICP22/47, which flank oriS, resulted in a greater than 80-fold decrease in origin function compared with a plasmid, pOS-822, which retains these sequences. In an effort to identify specific cis-acting elements responsible for this effect, we conducted systematic deletion analysis of the flanking region with plasmid pOS-822 and tested the resulting mutant plasmids for origin function. Stimulation by cis-acting elements was shown to be both distance and orientation dependent, as changes in either parameter resulted in a decrease in oriS function. Additional evidence for the stimulatory effect of flanking sequences on origin function was demonstrated by replacement of these sequences with the cytomegalovirus immediate-early promoter, resulting in nearly wild-type levels of oriS function. In competition experiments, cotransfection of cells with the test plasmid, pOS-822, and increasing molar concentrations of a competitor plasmid which contained the ICP4 and ICP22/47 transcriptional regulatory regions but lacked core origin sequences resulted in a significant reduction in the replication efficiency of pOS-822, demonstrating that factors which bind specifically to the oriS-flanking sequences are likely involved as auxiliary proteins in oriS function. Together, these studies demonstrate that trans-acting factors and the sites to which they bind play a critical role in the efficiency of HSV-1 DNA replication from oriS in transient-replication assays.
Recent Development of Polybenzoxazine (2004)

Synthesis or polyperization and modification of polybenzoxazines was reviewed. The future for development of polybenzoxazines was also dicussed.
Surface-plasmon resonance sensing of alcohol with electrodeposited polythiophene and gold nanoparticle-oligothiophene films (2005)

Electrodeposited films of polythiophene or gold nanoparticles (NPs) capped with conjugated oligothiophenes prepared on thin gold films are employed in a Kretschmann-type surface-plasmon resonance detector. The polythiophene films selectively respond to alcohol (ethanol or methanol) and toluene vapors but not to hexanes or water vapors, while the nanoparticle/oligothiophene films respond only to alcohol vapors of the solvents tested. For both films, the response to vapors consisted of the minimum in the reflectance curve (θ0) shifting to a higher angle as the thickness of the film increased. Slight increases in dielectric constant were also observed. The NPs do not result in an enhancement in sensitivity, contrary to theoretical predictions that suggest greater sensitivity may be achieved due to localized surface-plasmon effects associated with the presence of the Au NPs in the dielectric.
Fermentative Utilization of Glycerol by Escherichia coli and Its Implications for the Production of Fuels and Chemicals (2007)

Availability, low prices, and a high degree of reduction make glycerol an ideal feedstock to produce reduced chemicals and fuels via anaerobic fermentation. Although glycerol metabolism in Escherichia coli had been thought to be restricted to respiratory conditions, we report here the utilization of this carbon source in the absence of electron acceptors. Cells grew fermentatively on glycerol and exhibited exponential growth at a maximum specific growth rate of 0.040 +/- 0.003 h(-1). The fermentative nature of glycerol metabolism was demonstrated through studies in which cell growth and glycerol utilization were observed despite blocking several respiratory processes. The incorporation of glycerol in cellular biomass was also investigated via nuclear magnetic resonance analysis of cultures in which either 50% U-13C-labeled or 100% unlabeled glycerol was used. These studies demonstrated that about 20% of the carbon incorporated into the protein fraction of biomass originated from glycerol. The use of U-13C-labeled glycerol also allowed the unambiguous identification of ethanol and succinic, acetic, and formic acids as the products of glycerol fermentation. The synthesis of ethanol was identified as a metabolic determinant of glycerol fermentation; this pathway fulfills energy requirements by generating, in a redox-balanced manner, 1 mol of ATP per mol of glycerol converted to ethanol. A fermentation balance analysis revealed an excellent closure of both carbon (approximately 95%) and redox (approximately 96%) balances. On the other hand, cultivation conditions that prevent H2 accumulation were shown to be an environmental determinant of glycerol fermentation. The negative effect of H2 is related to its metabolic recycling, which in turn generates an unfavorable internal redox state. The implications of our findings for the production of reduced chemicals and fuels were illustrated by coproducing ethanol plus formic acid and ethanol plus hydrogen from glycerol at yields approaching their theoretical maximum.
MicroRNA and proteome expression profiling in early‐symptomatic α‐synuclein(A30P)‐transgenic mice (2008)

The α-synuclein has been implicated in the pathophysiology of Parkinson's disease (PD), because mutations in the alpha-synuclein gene cause autosomal-dominant hereditary PD and fibrillary aggregates of alpha-synuclein are the major component of Lewy bodies. Since presynaptic accumulation of α-synuclein aggregates may trigger synaptic dysfunction and degeneration, we have analyzed alterations in synaptosomal proteins in early symptomatic α-synuclein(A30P)-transgenic mice by two-dimensional differential gel electrophoresis. Moreover, we carried out microRNA expression profiling using microfluidic chips, as microRNA have recently been shown to regulate synaptic plasticity in rodents and to modulate polyglutamine-induced protein aggregation and neurodegeneration in flies. Differentially expressed proteins in α-synuclein(A30P)-transgenic mice point to alterations in mitochondrial function, actin dynamics, iron transport, and vesicle exocytosis, thus partially resembling findings in PD patients. Oxygen consumption of isolated brain mitochondria, however, was not reduced in mutant mice. Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases.
A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis (2011)

This study demonstrates the utility of using a potent and highly selective, orally bioavailable JAK2 inhibitor for the treatment of RA. Using a selective inhibitor of JAK2 rather than pan-JAK inhibitors avoids the potential complication of immunosuppression while targeting critical signaling pathways involved in autoimmune disease progression.
Somatic Mutation and Germline Variants of MINPP1, a Phosphatase Gene Located in Proximity to PTEN on 10q23.3, in Follicular Thyroid Carcinomas1 (2001)

Various genes have been identified to play a role in the pathogenesis of follicular thyroid tumors. Cowden syndrome is the only known familial syndrome with an increased risk of both follicular thyroid adenoma (FA) and carcinoma (FTC). Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors. Although somatic intragenic mutations in PTEN, which maps to 10q23.3, are rarely found in follicular tumors, loss of heterozygosity (LOH) of markers within 10q22-24 occurs in about 25%. Recently, another phosphatase gene, MINPP1, has been localized to 10q23.3. MINPP1 has the ability to remove 3-phosphate from inositol phosphate substrates, a function that overlaps that of PTEN. Because of this overlapping function with PTEN and the physical location of MINPP1 to a region with frequent LOH in follicular thyroid tumors, we considered it to be an excellent candidate gene that could contribute to the pathogenesis of follicular thyroid tumors. We analyzed DNA from tumor and corresponding normal tissue from 23 patients with FA and 15 patients with FTC for LOH and mutations at the MINPP1 locus. LOH was identified in four malignant and three benign tumors. One of these FTCs with LOH was found to harbor a somatic c.122C > T or S41L mutation. We also found two germline sequence variants, c.809A > G (Q270R) and IVS3 + 34T > A. The c.809A > G variant was found in only one patient with FA but not in patients with FTC or normal controls. More interestingly, IVS3 + 34T > A was found in about 15% of FA cases and normal controls but not in patients with FTC. These results suggest a role for MINPP1 in the pathogenesis of at least a subset of malignant follicular thyroid tumors, and MINPP1 might act as a low penetrance predisposition allele for FTC.
2006年度聚焦：创新连动（创新成果源于创新的方法） (2006)

短短几年前，逾半数的半导体消费均归功干企业用户，而日前，普通消费者已成为推动这一消费增长的主要推动力。从手机到电视，从计算机到汽车，当前消费者在半导体领域的需求占主导地位，市场竞争也比以往任何时候都更为激烈。竞争中成败与否取决干能否推出独树一帜的产品，而价格则是最重要的决定性因素。对系统制造商而言，这意味着必须展开激烈的市场“拼杀”，而且产品的生命周期则短得让人头疼。还没等你顾得上计算收入了多少钱，新的竞争对手已经从背后偷袭了，往往会推出更新、更好、更廉价的产品。
Telecommunication software validation using a synchronous approach (2002)

Telephone services and features provide a challenging application domain for the development and the validation of real-time software. This paper reviews our experiment on incremental validation of services and features which has been carried out in collaboration with CNET-France Telecom. Because of the well-known "feature interaction problem", telephone software can be considered as safety-critical software, and must exhibit qualities such as correctness and safety with very high assurance. For this class of software, the requirements engineering phase usually ends in a formal specification which is provided in some logic; therefore, the validation can be performed in a very rigorous and formal way using proof tools and/or specification-based testing techniques. Much critical software is reactive: it continuously reacts with its environment at its own speed. Therefore, it must satisfy some strong temporal causalities between external events, in order to bring about or maintain the desired relationships in the environment. We have developed a new approach for specification-based testing of synchronous reactive software and its associated environment. The specification language is LUSTRE, which is both a temporal logic and a synchronous data-flow programming language. We have successfully modelled a telecommunication system as a reactive software system; this allowed us to extensively apply our testing approach to this type of software. A synchronous model of a telecommunication system is described. A specification of the model is then given and the validation work is presented.
Essential cell biology : an introduction to the molecular biology of the cell (1998)

1. Introduction to cells 2. Chemical components of cells 3. Energy, catalysis, and biosynthesis 4. How cells obtain energy from food 5. Protein structure and function 6. DNA 7. From DNA to protein 8. Chromosomes and gene regulation 9. Genetic variation 10. DNA technology 11. Membrane structure 12. Membrane transport 13. Energy generation in mitochondria and chloroplasts 14. Intracellular compartments and transport 15. Cell communication 16. Cytoskeleton 17. Cell division 18. Cell-cycle control and cell death 19. Tissues
Identification and characterization of lipopolysaccharide in acetic acid bacteria. (2007)

LPS with macrophage-activating activity is present in acetic acid bacteria, routinely consumed by humans.
Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis. (2002)

The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be therapeutic. Moreover, a better understanding of ultrasound's mechanical mechanism could lead to a better understanding of how and when ultrasound should be employed as a therapeutic modality.
Quantitative Acetylome Analysis Reveals the Roles of SIRT1 in Regulating Diverse Substrates and Cellular Pathways (2012)

Despite of the progress in identifying many Lys acetylation (Kac) proteins, Kac substrates for Kac-regulatory enzymes remain largely unknown, presenting a major knowledge gap in Kac biology. Here we identified and quantified 4623 Kac sites in 1800 Kac proteins in SIRT1(+/+) and SIRT1(-/-) MEF cells, representing the first study to reveal an enzyme-regulated Kac subproteome and the largest Lys acetylome reported to date from a single study. Four hundred eighty-five Kac sites were enhanced by more than 100% after SIRT1 knockout. Our results indicate that SIRT1 regulates the Kac states of diverse cellular pathways. Interestingly, we found that a number of acetyltransferases and major acetyltransferase complexes are targeted by SIRT1. Moreover, we showed that the activities of the acetyltransferases are regulated by SIRT1-mediated deacetylation. Taken together, our results reveal the Lys acetylome in response to SIRT1, provide new insights into mechanisms of SIRT1 function, and offer biomarker candidates for the clinical evaluation of SIRT1-activator compounds.
Specific binding of a HeLa cell nuclear protein to RNA sequences in the human immunodeficiency virus transactivating region. (1989)

The transactivator protein, tat, encoded by the human immunodeficiency virus is a key regulator of viral transcription. Activation by the tat protein requires sequences downstream of the transcription initiation site called the transactivating region (TAR). RNA derived from the TAR is capable of forming a stable stem-loop structure and the maintenance of both the stem structure and the loop sequences located between +19 and +44 is required for complete in vivo activation by tat. Gel retardation assays with RNA from both wild-type and mutant TAR constructs generated in vitro with SP6 polymerase indicated specific binding of HeLa nuclear proteins to the TAR. To characterize this RNA-protein interaction, a method of chemical "imprinting" has been developed using photoactivated uranyl acetate as the nucleolytic agent. This reagent nicks RNA under physiological conditions at all four nucleotides in a reaction that is independent of sequence and secondary structure. Specific interaction of cellular proteins with TAR RNA could be detected by enhanced cleavages or imprints surrounding the loop region. Mutations that either disrupted stem base-pairing or extensively changed the primary sequence resulted in alterations in the cleavage pattern of the TAR RNA. Structural features of the TAR RNA stem-loop essential for tat activation are also required for specific binding of the HeLa cell nuclear protein.
Business class services over a GPON network (2006)

A gigabit passive optical network (GPON) network is an attractive way to deliver residential services because it is typically deployed in an unprotected mode, and therefore economical. Typically, businesses are served over a protected network and with tight tolerances of parameters such as jitter and wander. A GPON network can provide the reliability and performance expected for business services, but it must be carefully designed from the outset. Many neighborhoods consist of a mixture of residential homes and small businesses. The businesses are usually interspersed with the residential homes. A GPON network can easily provide an unprotected but economical fiber drop to homes for residential services such as high-speed Internet access or Internet protocol television (IPTV) services. On the other hand, businesses require redundancy for high reliability, and they are willing to pay a premium for their DS1 or DS3 service. The full service access network (FSAN) group's G.984 specification allows for several types of redundancy within the network. However, what this specification doesn't provide for are the network interactions to use this redundancy in an efficient manner. SONET requires a protection switch to take place within 50 ms of a fault condition for minimal impact to services. A GPON network providing businesses services should also be required to switch within a 50 ms window. This is a difficult requirement, but achievable if the network is designed accordingly. Consideration for switching between OLT cards and between ONT fiber ports is a critical part of this reliable network. Another consideration is how much degradation is introduced into the DS1s/E1s as they traverse the network. If multiple adaptations are involved they may introduce unwanted jitter or wander into the network, which could cause slips and other unwanted events leading to a less reliable service. This paper addresses how to provide a reliable GPON network for business service and a cost-effective GPON network for residential service simultaneously. The paper addresses protection mechanisms, DS1/E1 mapping into GPON GEM strategies, and timing and synchronization requirements for providing reliable business services over a GPON network. It also covers various topology methods for providing redundant equipment and facilities for business services and provides a summary of what some of the economic tradeoffs might be for such a network.
Factors Involved in theIn VitroFermentability of Short Carbohydrates in Static Faecal Batch Cultures (2012)

In recent years, research has focused on the positive effects of prebiotics on intestinal health and gut microbiota. The relationship between their chemical structure and their fermentation pattern by human intestinal microbiota is still not well understood. The aim of this study was to improve understanding of this relationship and identify factors that may be used to design galactooligosaccharides that reach more distal regions than commercial prebiotics which mainly target the proximal colon. The following factors were investigated: monomer type, linkage, substitution, and degree of polymerisation. Total organic acid production from sugars by faecal bacteria was fitted to a model which allowed an estimate of the time when half of the maximal organic acid concentration was reached ( T 50 ) in static faecal batch cultures. The different factors can be grouped by their effectiveness at prolonging fermentation time as follows: substitution is most effective, with methylgalactose,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math>-galactose-pentaacetate, D-fucose, and galactitol fermented more slowly than D-galactose. Monomers and linkage also influence fermentation time, with L rhamnose, arabinose, melezitose, and xylose being fermented significantly slower than D-glucose (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>), maltose, isomaltose, cellobiose, and gentiobiose showing that Glc<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>α</mml:mi></mml:mrow></mml:math>1-6Glc and Glc<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math>1-4Glc were utilised slowest. Chain length had the smallest effect on fermentation time.