gebhart/patrepeval huggingface dataset:
Comprehensive identification of Arabidopsis thaliana MYB transcription factors interacting with R/B‐like BHLH proteins (2004)

In-depth analysis of protein-protein interaction specificities of the MYB protein family of Arabidopsis thaliana revealed a conserved amino acid signature ([DE]Lx(2)[RK]x(3)Lx(6)Lx(3)R) as the structural basis for interaction between MYB and R/B-like BHLH proteins. The motif has successfully been used to predict new MYB/BHLH interactions for A. thaliana proteins, it allows to discriminate between even closely related MYB proteins and it is conserved amongst higher plants. In A. thaliana, the motif is shared by fourteen R2R3 MYB proteins and six 1R MYB proteins. It is located on helices 1 and 2 of the R3 repeat and forms a characteristic surface-exposed pattern of hydrophobic and charged residues. Single-site mutation of any amino acid of the signature impairs the interaction. Two particular amino acids have been determined to account for most of the interaction stability. Functional specificity of MYB/BHLH complexes was investigated in vivo by a transient DFR promoter activation assay. Residues stabilizing the MYB/BHLH interaction were shown to be critical for promoter activation. By virtue of proved and predicted interaction specificities, this study provides a comprehensive survey of the MYB proteins that interact with R/B-like BHLH proteins potentially involved in the TTG1-dependent regulatory interaction network. The results are discussed with respect to multi-functionality, specificity and redundancy of MYB and BHLH protein function.
Interpretation of knockout experiments: the congenic footprint (2007)

In gene targeting experiments, the importance of genetic background is now widely appreciated, and knockout alleles are routinely backcrossed onto a standard inbred background. This produces a congenic strain with a substantial segment of embryonic stem (ES)-cell-derived chromosome still flanking the knockout allele, a phenomenon often neglected in knockout studies. In cholecystokynin 2 (Cckbr) knockout mice backcrossed with C57BL/6, we have found a clear 'congenic footprint' of expression differences in at least 10 genes across 40 Mb sequence flanking the Cckbr locus, each of which is potentially responsible for aspects of the 'knockout' phenotype. The expression differences are overwhelmingly in the knockout-low direction, which may point to a general phenomenon of background dependence. This finding emphasizes the need for caution in using gene knockouts to attribute phenotypic effects to genes. This is especially the case when the gene is of unknown function or the phenotype is unexpected, and is a particular concern for large-scale knockout and phenotypic screening programmes. However, the impact of genetic background should not be simply viewed as a potential confound, but as a unique opportunity to study the broader responses of a system to a specific (genetic) perturbation.
Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis (2002)

Heparan sulfate glycosaminoglycans, present at the cell surface and in the extracellular matrix that surrounds cells, are important mediators of complex biological processes. Furthermore, it is now apparent that cells dynamically regulate the structure of their heparan sulfate "coat" to differentially regulate extracellular signals. In the present study, the importance of sequence information contained within tumor cell-surface heparan sulfate was investigated. Herein, we demonstrate that the heparan sulfate glycosaminoglycan coat present on tumor cells contains bioactive sequences that impinge on tumor-cell growth and metastasis. Importantly, we find that growth promoting as well as growth inhibiting sequences are contained within the polysaccharide coat. Furthermore, we find that the dynamic balance between these distinct polysaccharide populations regulates specific intracellular signal-transduction pathways. This study not only provides a framework for the development of polysaccharide-based anti-cancer molecules but also underscores the importance of understanding a cell's polysaccharide array in addition to its protein complement, to understand how genotype translates to phenotype in this post-genomic age.
Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function. (1994)

To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).
Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. (1987)

The objective of this study was to elucidate the close similarity in properties between endothelium-derived relaxing factor (EDRF) and nitric oxide radical (NO). Whenever possible, a comparison was also made between arterial and venous EDRF. In vascular relaxation experiments, acetylcholine and bradykinin were used as endothelium-dependent relaxants of isolated rings of bovine intrapulmonary artery and vein, respectively, and NO was used to relax endothelium-denuded rings. Oxyhemoglobin produced virtually identical concentration-dependent inhibitory effects on both endothelium-dependent and NO-elicited relaxation. Oxyhemoglobin and oxymyoglobin lowered cyclic guanosine monophosphate (cGMP) levels, increased tone in unrubbed artery and vein, and abolished the marked accumulation of vascular cGMP caused both by endothelium-dependent relaxants and by NO. The marked inhibitory effects of oxyhemoglobin on arterial and venous relaxant responses and cGMP accumulation as well as its contractile effects were abolished or reversed by carbon monoxide. These observations indicate that EDRF and NO possess identical properties in their interactions with oxyhemoproteins. Both EDRF from artery and vein and NO activated purified soluble guanylate cyclase by heme-dependent mechanisms, thereby revealing an additional similarity in heme interactions. Spectrophotometric analysis disclosed that the characteristic shift in the Soret peak for hemoglobin produced by NO was also produced by an endothelium-derived factor released from washed aortic endothelial cells by acetylcholine or A23187. Pyrogallol, via the action of superoxide anion, markedly inhibited the spectral shifts, relaxant effects, and cGMP accumulating actions produced by both EDRF and NO. Superoxide dismutase enhanced the relaxant and cGMP accumulating effects of both EDRF and NO. Thus, EDRF and NO are inactivated by superoxide in a closely similar manner. We conclude, therefore, that EDRF from artery and vein is either NO or a chemically related radical species.
Bipyridine Periodic Mesoporous Organosilica: A Solid Ligand for the Iridium‐Catalyzed Borylation of CH Bonds (2014)

Abstract With the goal to obtain a molecularly defined iridium(I) heterogeneous CH functionalization catalyst, a periodic mesoporous organosilica (PMO) containing bipyridylene moieties in a matrix of biphenylene units as ligand platform was designed and fully characterized. The material exhibits a high surface area with small mesopores in a vermicular arrangement, and the pore walls show a highly crystal‐like character. After surface passivation with chlorotrimethylsilane and functionalization with chloro(1,5‐cyclooctadiene)iridium(I) dimer [{IrCl(COD)} 2 ] a molecularly defined Ir(I) surface complex was obtained according to EXAFS and UV‐Vis spectroscopy. This functionalized material catalyzes the direct CH borylation of arenes to yield the corresponding boronic esters and can be reused without significant loss of activity. magnified image
340 PRODUCTION OF TRANSGENIC PORCINE BLASTOCYSTS BY HANDMADE CLONING (2004)

The present study demonstrates the application of the recently developed handmade cloning (HMC) technique in production of transgenic porcine blastocysts. The HMC technique was originally established for bovine nuclear transfer (Vajta et al., 2003, Biol. Reprod. 68, 571–578), and has the advantages of being less demanding and more productive than traditional nuclear transfer techniques. Cumulus-oocyte complexes were aspirated from slaughterhouse ovaries and matured for 41 h. Subsequently, the cumulus cells were removed by pipetting in 1 mg mL-1 hyaluronidase in HEPES-buffered TCM-199; zonae pellucidae were removed by incubation in 2 mg mL-1 pronase in HEPES-buffered TCM-199 supplemented with 2% cattle serum (T2) for 1 min. Bisection was performed by hand under a stereomicroscope using a microblade in 5 µg mL-1 cytochalasin B in TCM-199 supplemented with 20% cattle serum (T20). Demi-oocytes were incubated in 5 µg mL-1 Hoechst 33342 in T20 for 10 min, followed by examination under UV light to select the halves containing no chromatin, i.e., the cytoplasts. Porcine fibroblasts harvested from an ear skin biopsy were transfected with pN1-EGFP (Clontech) using Lipofectamine (Gibco, Life Technologies). G418 selection (0.8 mg mL-1) was applied 48 h after transfection, and well separated G418-resistant cell colonies originating from a single transfected cell were isolated, expanded, and cryopreserved. Days before, nuclear transfer cells were grown to a confluent monolayer in DMEM supplemented with 10% FCS. Fusions were performed 43 h after start of maturation. One cytoplast was attached to one fibroblast in 500 µg mL-1 phytohemagglutinin dissolved in T2. In the fusion chamber, covered with fusion medium (0.3 M mannitol, 0.1 mM MgSO4, 0.05 mM CaCl2, and 0.01% PVA), one cytoplast-fibroblast pair was fused with one cytoplast in a single step. The fusions were performed with a double DC pulse of 65 V, each pulse for 20 µs and 0.1 s apart from each other. Successfully fused embryos were activated 1 h after the end of fusion by incubation in 2 µM calcium ionophore A23187 in T20 for 5 min followed by 3-h incubation in microdrops of culture medium (NCSU-23 with 4 mg mL BSA) containing 2 mM 6-dimethylaminopurine. Activated embryos were cultured individually in microdrops of culture medium for 7 days. In four independent experiments, 93% of attempted reconstructed embryos fused and survived activation (31/31, 15/23, 28/28, and 37/37, respectively). On Day 7 after activation, the blastocyst rates (per successfully reconstructed embryos) were 6% (2/31), and 7% (1/15), 7% (2/28), and 3% (1/37), respectively. Green Fluorescent Protein was expressed in all cells of the developing blastocysts. The results show that transgenic porcine blastocysts can be produced using HMC, and the technique may also be applied for the production of transgenic pigs.
Endocytic Function, Glycosaminoglycan Specificity, and Antibody Sensitivity of the Recombinant Human 190-kDa Hyaluronan Receptor for Endocytosis (HARE) (2004)

The human hyaluronan receptor for endocytosis (hHARE) mediates the endocytic clearance of hyaluronan (HA) and chondroitin sulfate from lymph fluid and blood. Two hHARE isoforms (190 and 315 kDa) are present in sinusoidal endothelial cells of liver, spleen, and lymph nodes (Zhou, B., McGary, C. T., Weigel, J. A., Saxena, A., and Weigel, P. H. (2003) Glycobiology 13, 339-349). Here we report the specificity and function of the 190-kDa HARE, expressed without the larger isoform, in Flp-In 293 cell lines (190hHARE cells). Like the native protein, recombinant hHARE contains approximately 25 kDa of N-linked oligosaccharides, binds HA in a ligand blot assay, cross-reacts with three anti-rat HARE monoclonal antibodies, and is inactivated by reduction. The 190hHARE cell lines mediated rapid, continuous (125)I-HA endocytosis and degradation for >1 day. About 30-50% of the total cellular receptors were on the cell surface, and their recycling time for reutilization was approximately 8.5 min. The average K(d) for the binding of HA to the 190-kDa hHARE at 4 degrees C was 7 nm with 118,000 total HA binding sites per cell. Competition studies at 37 degrees C indicated that the 190-kDa hHARE binds HA and chondroitin better than dermatan sulfate and chondroitin sulfates A, C, D, and E, but it does not bind to heparin, heparan sulfate, or keratan sulfate. Although competition was observed at 37 degrees C, none of the glycosaminoglycans tested, except HA, competed for (125)I-HA binding by 190hHARE cells at 4 degrees C. Anti-HARE monoclonal antibodies #30 and #154, which do not inhibit (125)I-HA uptake mediated by the 175-kDa rat HARE, partially blocked HA endocytosis by the 190-kDa hHARE. We conclude that the 190-kDa hHARE can function independently of other hHARE isoforms to mediate the endocytosis of multiple glycosaminoglycans. Furthermore, the rat and human small HARE isoforms have different glycosaminoglycan specificities and sensitivities to inhibition by cross-reacting antibodies.
Synthetic Approaches to Vitamin D (1994)

This review describes the major synthetic approaches to the triene unit of vitamin D. In addition, various syntheses of two of the most important intermediates, dienoate (-)-18 and enyne (-)-32 as well as their close relatives, are presented. 1 Introduction 2. Construction of the Triene Unit of Vitamin D 2.1 Bond a Approach 2.1.1 A-ring Allylic Phosphine Oxide and CD-ring Grundmann Ketone (a) Lythgoe Approach (b) Hoffmann-La Roche Approach 2.1.2 A-ring Enyne and CD-ring Grundmann Ketone / Enol Triflate (a) Lythgoe Approach (b) Okamura Approach (c) Mouriño Approach 2.1.3 CD-ring Sulfone and A-ring Dienal (Umpolung Fashion) 2.2 Bond b Approach 2.2.1 CD-ring Methylene Sulfone and A-ring α,β- Unsaturated Ester / Aldehyde 2.2.2 Mazur Solvolysis of Cyclovitamin D3 (a) Fukumoto and Kametani Approach (b) Wilson Approach 2.2.3 Palladium-catalyzed Cyclization and Coupling (a) Trost Approach (b) Nuss Approach 2.3 Bond c Approach 2.3.1 Lythgoe Approach 2.3.2 Takano Approach 3 Syntheses of Important A-ring Intermediates 3.1 Syntheses of Dienoate (-)-18 and Its Relatives 3.1.1 Posner Approach 3.1.2 Shimizu Approach 3.1.3 Crich Approach 3.1.4 Hoffmann-La Roche Approach 3.1.5 Kobayashi Approach 3.1.6 Takano Approach 3.2 Syntheses of Enyne (-)-32 and Its Relatives 3.2.1 Lythgoe Approach 3.2.2 Desmaele Approach 3.2.3 Hoffmann-La Roche Approach 3.2.4 Mouriño Approach 3.2.5 Okamura Approach 3.2.6 Takano Approach 4 Conclusions
Inhibition of HIV Fusion with Multivalent Gold Nanoparticles (2008)

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.
Properties and Reactions of Substituted 1,2‐Thiazetidine 1,1‐Dioxides: Methylation of β‐Sultams (1991)

Abstract Methylation of N ‐substituted 1,2‐thiazetidine 1,1‐dioxides in the presence of lithium diisopropylamide (LDA) yields 4,4‐dimethyl derivatives. Monomethylation only occurs when one position at C‐4 is blocked by a silyl group, which, afterwards, can be removed by treatment with tetrabutylammonium fluoride (TBAF). A silyl protecting group at the nitrogen is easily removed by cleavage with TBAF on silica gel under mild conditions.
Effective n-type doping of monolayer MoS<inf>2</inf> by AlO<inf>x</inf> (2017)

Doping of two-dimensional (2D) semiconductors often utilizes charge transfer techniques that are not compatible with standard CMOS fabrication and are unstable over time. Sub-stoichiometric oxides have demonstrated stable 2D material doping [1], but often degrade the subthreshold swing (S) and current on/off ratio (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> /I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</sub> ) of a device. Here, we demonstrate that AlO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> can n-dope monolayer (1L) MoS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> while preserving I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> /I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</sub> and S. The AlO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> doping significantly reduces the contact resistance (to 480 Ω·μm) while preserving the mobility (~34 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> V <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> s <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> ) and S, ultimately achieving record on-current of 700 μA/μm for a monolayer semiconductor. We also present a model for the effect of interface traps on the transfer characteristics, which explains the experimentally obtained results.
Antiproliferative Effect of c-myc Antisense Phosphorothioate Oligodeoxynucleotides in Malignant Glioma Cells (1997)

These results suggest that c-Myc plays a critical role in glioma cell proliferation and demonstrate that antisense ODNs can suppress proto-oncogene expression and inhibit the proliferation of glioma cells. Our results indicate that the antiproliferative activity of these ODNs was mediated predominantly through sequence-specific antisense mechanisms, but that sequence-specific nonantisense effects may also contribute to the strongest effects demonstrated. These findings support a potential role for antisense strategies designed to inhibit c-myc expression in the treatment of malignant gliomas.
Optimization of Process Conditions for Infected Animal Tissues by Alkaline Hydrolysis Technology (2016)

Alkaline hydrolysis represents a relatively new animal carcass disposal technology. It uses alkali, high temperature and high pressure to catalyze the hydrolysis of biological materials into a sterile aqueous solution and bone residues. The purpose of this work is to provide a complete study of the influence of operational parameters on alkaline hydrolysis process and to find an optimal combination of factors that maximize the disposal efficiency. In order to determine the optimal combination of the four factors viz. treatment time, temperature, the concentration of alkali solution and the ratio of alkali and tissue, single-factor and orthogonal experiments were used. The orthogonal experimental design included four variables (three levels) in L9 orthogonal array. Results showed that four factors all significantly (P < 0.01) increased the efficiency of alkaline hydrolysis. The order of significance decreased from temperature, alkali concentration, the ratio of alkali and tissue to treatment time. Optimum process conditions were found to be as follows: treatment time, 180 min; temperature, 150 °C; the concentration of alkali solution, 5% and the ratio of alkali and tissue, 3 mL/g. The optimum conditions was validated and proven to be reliable for achieving the complete hydrolysis of different animal tissues and the inactivation of Bacillus stearothermophilus. This study provides a biosafety disposal method of infected animal tissues and be useful to establish effective process conditions of alkaline hydrolysis.
Cerebrospinal Fluid β-Amyloid(1-42) in Alzheimer Disease (1999)

The sensitivity of CSF-beta-amyloid(1-42) level as a diagnostic marker for AD is high. The intra-individual biological variation in CSF-beta-amyloid(1-42) level is low. Low CSF-beta-amyloid(1-42) levels are also found in the earlier stages of dementia in patients with AD. These findings suggest that CSF-beta-amyloid(1-42) analyses may be of value in the clinical diagnosis of AD, especially in the early course of the disease, when drug therapy may have the greatest potential of being effective but clinical diagnosis is particularly difficult.
Managing the open abdomen. (2004)

Control of intra-abdominal fluid secretion, facilitation of abdominal exploration, and preservation of the fascia for abdominal wall closure is a major challenge in the management of patients with an open abdomen. Studies comparing different protocols of care have not been conducted and frequency of exploration, surgical procedures, and indications for definitive closure are generally based on clinical judgment. Morbidity and mortality rates are high. Vacuum-assisted therapy has been reported to help meet the challenges of managing the open abdomen and is particularly useful in patients with abdominal compartment syndromes, traumatic injuries, and severe intra-abdominal sepsis. Over the years, clinicians have developed various approaches to achieve vacuum-assisted closure using wall suction. Some disadvantages of the wall-suction methods are eliminated when using more recently developed vacuum therapy devices. These devices apply subatmospheric pressure, reducing bowel edema, bacterial counts, and inflammatory substances found in open abdominal wounds while eliminating the need for frequent dressing changes, maintaining intact skin, and improving fluid management. The results of six case studies presented are encouraging, suggesting that this treatment approach is safe and effective. Controlled clinical studies to establish the safety and effectiveness of this treatment approach and to facilitate the development of treatment guidelines are needed to help manage an increasingly common group of patients who might benefit from this treatment approach.
Expression cloning of a cDNA encoding the murine interleukin 4 receptor based on ligand binding. (1990)

Interleukin 4 (IL-4) is a potent mediator of growth and differentiation for various lymphoid and myeloid cells. To isolate a cDNA encoding the murine IL-4 receptor, we have developed an expression cloning method that uses biotinylated ligand as a probe and that may be generally applicable to cloning of receptor genes. COS-7 cells transiently transfected with the cloned full-length cDNA bind murine IL-4 specifically with a Kd = 165 pM. Crosslinking of 125I-labeled IL-4 to COS-7 cells transfected with the cDNA reveals binding to proteins of 120-140 kDa. IL-4-responsive cells also express IL-4-binding proteins of 120-140 kDa but show additional bands at 60-70 kDa; the relationship of the smaller proteins to the larger ones is unclear. The nucleotide sequence indicates that the full-length cDNA encodes 810 amino acids including the signal sequence. While no consensus sequence for protein kinases is present in the cytoplasmic domain, a sequence comparison with the erythropoietin receptor, the IL-6 receptor, and the beta chain of the IL-2 receptor reveals a significant homology in the extracellular domain, indicating that the IL-4 receptor is a member of a cytokine receptor family.