gebhart/patrepeval huggingface dataset:
Coupling of Monoclonal Antibodies with Biotin (2003)

The avidin-biotin bond is the strongest known biological interaction between a ligand and a protein (K d = 1.3 × 10−15 M at pH 5) (1). The affinity is so high that the avidin-biotin complex is extremely resistant to any type of denaturing agent (2). Biotin (Fig. 1) is a small, hydrophobic molecule that functions as a coenzyme of carboxylases (3). It is present in all living cells. Avidin is a tetrameric glycoprotein of 66,000–68,000 mol wt, found in egg albumin and in avian tissues. The interaction between avidin and biotin occurs rapidly, and the stability of the complex has prompted its use for in situ attachment of labels in a broad variety of applications, including immunoassays, DNA hybridization (4–6), and localization of antigens in cells and tissues (7). Avidin has an isoelectric point of 10.5. Because of its positively charged residues and its oligosaccharide component, consisting mostly of mannose and glucosamine (8), avidin can interact nonspecifically with negative charges on cell surfaces and nucleic acids, or with membrane sugar receptors. At times, this causes background problems in histochemical and cytochemical applications. Streptavidin, a near-neutral, biotin binding protein (9) isolated from the culture medium of Streptomyces avidinii, is a tetrameric nonglycosylated analog of avidin with a mol wt of about 60,000. Like avidin, each molecule of streptavidin binds four molecules of biotin, with a similar dissociation constant. The two proteins have about 33% sequence homology, and tryptophan residues seem to be involved in their biotin binding sites (10,11). In general, streptavidin gives less background problems than avidin. This protein, however, contains a tripeptide sequence Arg-Tyr-Asp (RYD) that apparently mimics the binding sequence of fibronectin Arg-Gly-Asp (RGD), a universal recognition domain of the extracellular matrix that specifically promotes cell adhesion. Consequently, the streptavidin-cell-surface interaction causes high background in certain applications (12).
GENERAL SELECTION FOR SPECIFIC DNA-BINDING ACTIVITIES (1986)

We present a general strategy for the selection of bacterial clones that express DNA-binding activities corresponding to particular DNA recognition sites. The selection uses a "challenge phage" vector, P22 Kn9 arc-amH1605, into which is substituted a synthetic DNA-binding site for a site that controls transcription of the P22 antirepressor (ant) gene. Constitutive synthesis of antirepressor channels a challenge phage into lytic development and efficiently kills an infected host, unless the substituted site is bound by a specific protein; in this case, the challenge phage prefers lysogenic development, and the host survives and acquires an antibiotic-resistance phenotype. Infections with challenge phages carrying the E. coli Lac operator, phage lambda OL1 operator, or synthetic, "idealized" E. coli Trp and Tn10 Tet operators select clones that express each of the corresponding binding activities. The use of challenge phage vectors may be extended to select clones that express eukaryotic DNA-binding activities.
A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome (2016)

Broad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome.
Long-term treatment of Laron type dwarfs with insulin-like growth factor-1 increases serum insulin-like growth factor-binding protein-3 in the absence of growth hormone activity (1993)

Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of insulin-like growth factor I (IGF-I) in serum, and its production is growth hormone (GH) dependent. It is unclear whether in humans IGFBP-3 production is directly regulated by GH or mediated via IGF-I. We addressed this question in six patients with Laron-type dwarfism, a syndrome characterized by the absence of GH receptor activity (LTD), who were chronically treated with recombinant IGF-I. Analysis of the electrophoretic profiles of serum IGFBPs in these patients by Western ligand blotting revealed an extremely low IGFBP-3 level. A striking progressive increase in serum IGFBP-3 was observed with continuous treatment, despite the absence of GH action. In LTD children, serum IGFBP-3 increased up to 19-fold after six months of therapy and equalled levels observed in controls, whereas in adult LTD patients the increase was smaller. A rise in serum levels of 34, 30 and 24 kDa BPs (presumably IGFBP-2, -1 and -4, respectively was also noted with chronic IGF-I therapy. This proof of GH-independent induction of IGFBP-3 by IGF-I may be a major advantage in the therapeutic use of biosynthetic IGF-I in several types of short stature children.
Mild cognitive impairment in the elderly (2002)

The present review on mild cognitive impairment (MCI) concerns preclinical Alzheimer's disease (no cognitive impairment but neuropathological changes typical for Alzheimer's disease), subjective cognitive/memory complaints with and without verified neuropsychological deficit, and the validity of amnestic MCI. The following were shown to be predictors of Alzheimer's disease: measures of episodic memory; presence of the apolipoprotein E ε4 allele; reduced cerebral temporo-parietal glucose metabolism and blood flow; neuronal loss in the entorhinal cortex, and in layer II and CA1 of the hippocampus; brain activation of the hippocampus through cognitive stress tests (as measured using structural and functional magnetic resonance imaging); and purely subjective cognitive impairment and features of age-associated cognitive decline. Furthermore, the distinction of MCI from both healthy and demented status, and the role of activities of daily living in MCI are emphasized. Early predictors and three stages (MCI spectrum disorder) in the development of Alzheimer's disease are discussed: asymptomatic Alzheimer's disease (including preclinical Alzheimer's disease), purely subjective cognitive complaints, and objective evidence of MCI.
Phenotypic and functional analysis of peripheral blood lymphocytes during interferon-alpha 2b therapy in multiple myeloma patients with low tumor mass. (1992)

i) IFN-alpha in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-alpha therapy.
Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. (1993)

These observations indicate that ACE protein is increased within the myocardium of LVH hearts, extending recent findings of increased cardiac ACE activity and mRNA levels in this model of pressure-overload LVH in the rat. Blockade of the enzyme by an ACE inhibitor decreases intracardiac Ang I-to-Ang II conversion rate and prevents the functional changes of Ang I-to-Ang II activation
HOXB4 Overexpression Promotes Hematopoietic Development by Human Embryonic Stem Cells (2006)

Human embryonic stem cells (hESCs) are a potential source of hematopoietic cells for therapeutic transplantation and can provide a model for human hematopoiesis. Culture of hESCs on murine stromal layers or in stromal-free conditions as embryoid bodies results in low levels of hematopoietic cells. Here we demonstrate that overexpression of the transcription factor HOXB4 considerably augments hematopoietic development of hESCs. Stable HOXB4-expressing hESC clones were generated by lipofection and could be maintained in the undifferentiated state for prolonged passages. Moreover, differentiation of hESCs as embryoid bodies in serum-containing medium without the use of additional cytokines led to sequential expansion of first erythroid and then myeloid and monocytic progenitors from day 10 of culture. These cells retained the capacity to develop into formed blood elements during in vitro culture. Consistent with the development of committed hematopoietic cells, we observed the expression of transcription factors known to be critical for hematopoietic development. We thus demonstrate successful use of enforced gene expression to promote the differentiation of hESCs into a terminally differentiated tissue, thereby revealing an important role for HOXB4 in supporting their in vitro development along the hematopoietic pathway.
Integrated in situ genetic analyzer for microbiology in extreme environments (2011)

In this study, a totally integrated in situ analyzer for microbial gene detection has been developed for oceanography applications. A PDMS–glass microfluidic device that is capable of cell lysis, DNA purification, PCR, and optical detection has been utilized as the core element of the in situ analyzer. Microbial genomic DNA is purified and concentrated on glass beads packed in the microfluidic device. PCR is performed in a flow-through manner, and the amplified products are fluorescently detected using optical fibers. The sensitivity of a completed analyzer with deep-sea operation capabilities has been evaluated in a laboratory setting, and the analyzer has been operated in real deep-sea environments. Field evaluations have shown that the amplification of the eubacterial universal 16S rRNA gene and the recovery of the PCR product to the surface are successfully achieved in deep-sea environments.
LiCl-Mediated Preparation of Highly Functionalized Benzylic Zinc Chlorides (2008)

In the presence of zinc dust (1.5−2.0 equiv) and LiCl (1.5−2.0 equiv), various benzylic chlorides bearing functional groups (iodide, cyanide, ester, ketone) are smoothly converted at 25 °C to the corresponding zinc reagents without homo-coupling (<5%). The utility of these benzylic zinc reagents is demonstrated by a short synthesis of papaverine.
Fragmentation pathways of metopimazine and its metabolite using ESI‐MSn, HR‐MS and H/D exchange (2010)

Metopimazine (MPZ) is a phenothiazine derivative used to prevent emesis during chemotherapy where few structural analysis of the aforementioned compound have been described in the literature. Thus, this work reports, for the first time, the detailed study of fragmentation pathways of MPZ and its metabolite (AMPZ) using electrospray ionization (EI) with multistage mass spectrometry (ESI-MS(n)) in positive-ion mode. The structures of 21 product ions were identified and their accurate masses were determined using high resolution mass spectrometry (HRMS) experiments. Characteristic product ions of these two phenothiazine derivatives are more particularly displayed along with differences between their relative abundances and their structures checked by H/D exchange experiments.
Transport and assembly of nanowires in suspension (2006)

Nanowires are potentially important constituents for nanoscale devices. Manipulation of nanowires in suspension in order to assemble them for device applications has been a formidable problem. Previously most methods have involved the use of external magnetic fields acting on magnetic nanowires. Using ac electric fields applied to strategically designed microelectrodes, we show how nanowires, both magnetic and nonmagnetic, in suspension can be driven to align, to chain, to accelerate in directions parallel and perpendicular to its orientation, to concentrate onto designated places, and to disperse in a controlled manner with high efficiency despite an extremely low Reynolds number (of the order of 10<sup>-5</sup>). This method of manipulating nanowires can also be applied to other small elongated entities such as carbon nanotubes.
Short and Straightforward Synthesis of (−)-1-Deoxygalactonojirimycin (2010)

The mildness and low basicity of vinylzinc species functioning as a nucleophile in addition to alpha-chiral aldehydes is characterized by lack of epimerization of the vulnerable stereogenic center. This is demonstrated by a highly diastereoselective synthesis of 1-deoxygalactonojirimycin in eight steps from commercial starting materials with overall yield of 35%.
Constrained Corticotropin Releasing Factor Antagonists (Astressin Analogues) with Long Duration of Action in the Rat (1999)

In an earlier report we identified specific modifications and substitutions of corticotropin releasing factor (CRF) that led to the discovery of antagonists with extended duration of action as compared to that of astressin {cyclo(30-33)[DPhe(12),Nle(21),Glu(30), Lys(33),Nle(38)]hCRF((12)(-)(41))}. These additional modifications included elongation of the peptide chain by three residues at the N-terminus, its acetylation, and the [CalphaMeLeu(27)] substitution to yield cyclo(30-33)[DPhe(12), Nle(21),CalphaMeLeu(27),Glu(30), Lys(33),Nle(38)]Ac-hCRF((9)(-)(41)), which was found to be longer acting than astressin (Rivier, J.; et al. J. Med. Chem. 1998, 41, 5012-5019). To further increase the efficiency (potency, duration of action, and bioavailability) of this family of antagonists, we introduced two or more CalphaMe-leucine residues at positions shown in earlier studies to be favorable (Hernandez, J.-F.; et al. J. Med. Chem. 1993, 36, 2860-2867). Whereas the introduction of CalphaMe-leucine residues at positions 27 and either 18 (11), 37 (17), or 40 (19) resulted in dramatic increases in duration of inhibitory action in the adrenalectomized (adx) rat after intravenous injection, the same substitution at positions 27 and either 15 (7, 8), 17 (9), 19 (12, 13), or 41 (20) led to short acting analogues. Other substitutions by CalphaMeLeu at positions 27 and either 10 (4), 13 (5), 14 (6), 21 (14), 24 (15), 36 (16), or 38 (18) yielded analogues with duration of action intermediate between those mentioned above. Cyclo(30-33)[DPhe(12), Nle(21), CalphaMeLeu(27),Glu(30),Lys(33),Nle(38), CalphaMeLeu(40)]Ac-hCRF((9)(-)(41)) (astressin B, 19) was one of the most efficacious analogues of this series (>4 h inhibition of ACTH secretion at 25 microgram/adx rat). It was found to be even longer acting via subcutaneous administration in either an aqueous (>24 h inhibition of ACTH secretion at 100 microgram/adx rat) or lipid milieu (DMSO/peanut oil, >24 h inhibition of ACTH secretion at 30 microgram/adx rat) than after intravenous administration (<12 h inhibition of ACTH secretion at 100 microgram/adx rat). We concluded that Calpha-methylation at some positions may favor a bioactive conformation while also preventing degradation and/or elimination, resulting in significant extension of duration of action.
Bigtable (2008)

Bigtable is a distributed storage system for managing structured data that is designed to scale to a very large size: petabytes of data across thousands of commodity servers. Many projects at Google store data in Bigtable, including web indexing, Google Earth, and Google Finance. These applications place very different demands on Bigtable, both in terms of data size (from URLs to web pages to satellite imagery) and latency requirements (from backend bulk processing to real-time data serving). Despite these varied demands, Bigtable has successfully provided a flexible, high-performance solution for all of these Google products. In this article, we describe the simple data model provided by Bigtable, which gives clients dynamic control over data layout and format, and we describe the design and implementation of Bigtable.
Using Gene Expression Noise to Understand Gene Regulation (2012)

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a major source of this variability, and its physiological consequences have been topics of intense research for the last decade. Several recent studies have measured variability in protein and messenger RNA levels, and they have discovered strong connections between noise and gene regulation mechanisms. When integrated with discrete stochastic models, measurements of cell-to-cell variability provide a sensitive "fingerprint" with which to explore fundamental questions of gene regulation. In this review, we highlight several studies that used gene expression variability to develop a quantitative understanding of the mechanisms and dynamics of gene regulation.
Effects of Tetramethoxystilbene on Hormone-Resistant Breast Cancer Cells: Biological and Biochemical Mechanisms of Action (2007)

Secondary resistance to hormonal therapy for breast cancer commonly develops after an initial response to tamoxifen or aromatase inhibitors. Agents to abrogate these adaptive changes would substantially enhance the long-term benefits of hormonal therapy. Our studies with a stilbene derivative called TMS (2,3',4,5'-tetramethoxystilbene) identified unexpected effects with potential utility for treatment of breast tumors secondarily resistant to hormonal therapy. TMS was originally developed as an inhibitor of cytochrome P450 1B1 to block the conversion of estradiol to 4-OH-estradiol. While studying this agent in three models of hormone resistance, we detected direct antitumor effects not related to its role as an inhibitor of catecholestrogens. During examination of the mechanisms involved, we showed that treatment with 3 micromol/L TMS for 24 h inhibited tubulin polymerization and microtubule formation, caused a cell cycle block at the G2-M phase, and induced apoptosis. TMS also inhibited activated focal adhesion kinase (FAK), Akt, and mammalian target of rapamycin (mTOR) and stimulated c-jun-NH2-kinase and p38 mitogen-activated protein kinase activity. With respect to antitumor effects, TMS at a concentrations of 0.2 to 0.3 micromol/L inhibited the growth of long-term tamoxifen-treated MCF-7 cells by 80% and fulvestrant-treated MCF-7 cells by 70%. In vivo studies, involving 8 weeks of treatment with TMS via a 30-mg s.c. implant, reduced tumor volume of tamoxifen-resistant MCF-7 breast cancer xenografts by 53%. Our data suggest that TMS is a promising therapeutic agent because of its unique ability to block several pathways involved in the development of hormone resistance.
Apoptosis in human retinal degenerations. (1996)

Apoptosis is 1 of the important pathways of photoreceptor cell degeneration in pathologic myopia and age-related macular degeneration.
Dropwise condensation on superhydrophobic surfaces with two-tier roughness (2007)

Dropwise condensation can enhance heat transfer by an order of magnitude compared to film condensation. Superhydrophobicity appears ideal to promote continued dropwise condensation which requires rapid removal of condensate drops; however, such promotion has not been reported on engineered surfaces. This letter reports continuous dropwise condensation on a superhydrophobic surface with short carbon nanotubes deposited on micromachined posts, a two-tier texture mimicking lotus leaves. On such micro-/nanostructured surfaces, the condensate drops prefer the Cassie state which is thermodynamically more stable than the Wenzel state. With a hexadecanethiol coating, superhydrophobicity is retained during and after condensation and rapid drop removal is enabled.
BCR-ABL–induced adhesion defects are tyrosine kinase–independent (2002)

The t(9;22) chromosomal translocation results in expression of P210(BCR-ABL), a fusion protein necessary for the development of chronic myelogenous leukemia (CML). The constitutive activation of the P210(BCR-ABL) tyrosine kinase results in phosphorylation of multiple signaling pathways leading to the transformed phenotype. Additionally, extracellular interactions between P210(BCR-ABL)-expressing progenitor cells and bone marrow stroma may provide external signals that facilitate CML development. In contrast to the intracellular signaling pathways involved in CML, little is known about how P210(BCR-ABL) expression modifies cell-cell and cell-substratum interactions. To investigate the role of P210(BCR-ABL) in modulating cellular adhesion, we used a highly sensitive and quantitative cell detachment apparatus that measures the strength of association between a population of cells and an adhesive matrix. Our findings show that P210(BCR-ABL) expression increased adhesion nearly 2-fold between the myeloblastic cell line, 32D, and fibronectin compared to a control vector. We then investigated whether abnormal adhesion due to P210(BCR-ABL) expression was caused by its tyrosine kinase activity. A quantitative analysis of cell-fibronectin adhesion found that neither expression of a kinase-inactive P210(BCR-ABL) mutant in 32D cells or attenuation of kinase activity by STI571 (imatinib mesylate) in 32D cells transduced with wild-type P210(BCR-ABL) could correct the nearly 2-fold increase in cell-fibronectin adhesion. Similarly, STI571 treatment of Meg-01 cells, a P210(BCR-ABL)-expressing cell line derived from a patient in blast crisis, failed to inhibit adhesion to fibronectin. Together, our results indicate that changes in adhesion induced by P210(BCR-ABL) are independent of its tyrosine kinase activity.
Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus (2000)

This is the first report of IL-10 antagonist administration to humans. The study shows the involvement of IL-10 in the pathogenesis of SLE, and indicates that the use of IL-10 antagonists may be beneficial in the management of refractory SLE.
Innovative Management of Atrial Fibrillation (2005)

List of Contributors. Preface. Part I. On the Atrial Substrate. Chapter 1. Electrophysiologic Basis of Atrial Fibrillation. Chapter 2. Neurological Basis of Atrial Fibrillation. Chapter 3. Mechanical Basis of Atrial Fibrillation. Chapter 4. Molecular Basis of Atrial Fibrillation. Chapter 5. Atrial Plasticity. Part II. Developing Strategies for AF Management. Chapter 6. AV Node Ablation. Chapter 7. Percutaneous Atrial Catheter Ablation. Chapter 8. Implantable Device Therapy. Chapter 9. Surgical Ablation Therapy I. Maze Procedure. Chapter 10. Surgical Ablation Therapy II. Endocardium-Based Catheter Ablation. Chapter 11. Surgical Ablation Therapy III. Epicardium-Based Catheter Ablation. Chapter 12. Modification of the Left Atrial Appendage. Part III. Potential Areas of Opportunity for AF Management. Chapter 13. Transpericardial Therapy. Chapter 14. Gene Therapy. Chapter 15. Tissue Engineering. Index