gebhart/patrepeval huggingface dataset:
Differential regulation of the mcb and emr operons of Escherichia coli: role of mcb in multidrug resistance (1996)

The mcb operon (which is responsible for microcin B17 production) and the emr operon (which encodes a multidrug resistance pump) share a common negative regulator, EmrR. Nevertheless, compounds that induce the emr operon repress the mcb operon. The pump dedicated to microcin B17 extrusion can also protect the calls against sparfloxacin and other toxic compounds.
Synthesis and Reactivity of 7-Azaindoles (1H-Pyrrolo(2,3-b)pyridine) (2001)

The results of research into the chemistry of 7-azaindole during the last twenty years are presented. New synthetic methods for the 7-azaindole structures are developed including palladium-catalysed cross-coupling reactions. Reactivity of 3-formyl-, 3-halogeno- and 2-lithio-7-azaindole derivatives is reported. Functionalisation of the pyridine ring via the N-oxide is also described. In the last part, biological activity of various 7-azaindole derivatives is briefly indicated. Keywords: Azaindoles, palladium-catalysed, cross-coupling reactions, Kirkpatrickia varialosa, pyrrolo annelation, heteroatomic rings, butylcarbonylaminopyridine, photo-Graebe-Ullmann, intramolecular cyclisation, iminophosphorane moiety., functionalised aldehyde, iodomethame, monobrominated
Synthesis of a Bifunctional Monophosphinate DOTA Derivative Having a Free Carboxylate Group in the Phosphorus Side Chain (2008)

A new bifunctional cyclen-based ligand, 3-[hydroxy({4,7,10-tris[(tert-butoxycarbonyl)methyl]-1,4,7,10-tetraazacyclododecan-1-yl}methyl)phosphoryl]propanoic acid, was synthe-sized by alkylation of tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (t-Bu3DO3A) by ethyl 3-{ethoxy[(mesyloxy)methyl]phosphoryl}propanoate [MsOCH2P(O)(OEt)CH2CH2CO2Et]. The ethyl carboxylate group in the side chain was selectively deprotected to obtain the esterified bifunctional ligand. More efficient syntheses of some phosphinopropanoic acid derivatives were devised and the phosphorus alkylation reagent was prepared starting from hypophosphorus acid or its salt.
G-protein alpha o subunit: mutation of conserved cysteines identifies a subunitcontact surface and alters GDP affinity. (1993)

The reversible association of alpha and beta gamma subunits of GTP-binding proteins is important for signal transmission from a variety of cell-surface receptors to intracellular effectors. Previous work showed that 1,6-bis(maleimido)hexane, which crosslinks cysteine residues, crosslinks alpha o and alpha i-1 to beta gamma. These crosslinks are likely to form through a conserved cysteine because 1,6-bis(maleimido)hexane can also crosslink alpha i-2, alpha 1, alpha s and Drosophila alpha 1 to give products of the same apparent molecular weight as crosslinked alpha o beta gamma and alpha i-1 beta gamma. These proteins have only two cysteines in common. Therefore, we mutated each of the two conserved cysteines of alpha o to alanines. Mutation of Cys215 prevents crosslinking to beta gamma, but does not affect binding of guanosine 5'-[gamma-thio]triphosphate or the ability of the mutated alpha subunit to bind beta gamma. In models of the alpha subunit based on the crystal structure of p21ras, Cys215 is located on the face opposite to the GTP-binding site and near an area that changes conformation depending on the nucleotide bound. This surface on the alpha subunit overlaps a putative effector binding region, raising important questions about the spatial organization of the proteins as they form ternary complexes. Mutation of Cys325 has no effect on crosslinking but, surprisingly, decreases by a factor of 10 the affinity of the mutated protein for GDP, relative to wild type, without changing the affinity for guanosine 5'-[gamma-thio]triphosphate. This mutation falls within a region thought to contact receptors and may represent a site through which receptors enhance the release of GDP.
Contribution of sequence variation inDrosophilaactins to their incorporation into actin-based structures in vivo (2005)

Actin is a highly conserved protein important for many cellular functions including motility, contraction in muscles and intracellular transport. Many eukaryotic genomes encode multiple actin protein isoforms that differ from each other by only a few residues. We addressed whether the sequence differences between actin paralogues in one species affect their ability to integrate into the large variety of structures generated by filamentous actin. We thus ectopically expressed all six Drosophila actins as fusion proteins with green fluorescent protein (GFP) in a variety of embryonic, larval and adult fly tissues. We found that each actin was able to integrate into most actin structures analysed. For example, in contrast to studies in mammalian cells, the two Drosophila cytoplasmic actins were incorporated into muscle sarcomeres. However, there were differences in the efficiency with which each actin was incorporated into specific actin structures. The most striking difference was observed within the Z-lines of the sarcomeres: one actin was specifically excluded and we mapped this feature to one or both of two residues within the C-terminal half of the protein. Thus, in Drosophila, the primary sequence of different actins does affect their ability to incorporate into actin structures, and so specific GFPactins may be used to label certain actin structures particularly well.
Recent Advances in the Discovery of Small Molecule Inhibitors of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a Therapeutic Target for Inflammation and Oncology Disorders (2014)

IRAK4, a serine/threonine kinase, plays a key role in both inflammation and oncology diseases. Herein, we summarize the compelling biology surrounding the IRAK4 signaling node in disease, review key structural features of IRAK4 including selectivity challenges, and describe efforts to discover clinically viable IRAK4 inhibitors. Finally, a view of knowledge gained and remaining challenges is provided.
Identification of a Palmitic Acid-modified Form of Human Sonic hedgehog (1998)

During hedgehog biosynthesis, autocatalytic processing produces a lipid-modified amino-terminal fragment (residues 24-197 in the human Sonic hedgehog sequence) that is responsible for all known hedgehog signaling activity and that is highly conserved evolutionarily. Published in vitro biochemical studies using Drosophila hedgehog identified the membrane anchor as a cholesterol, and localized the site of attachment to the COOH terminus of the fragment. We have expressed full-length human Sonic hedgehog in insect and in mammalian cells and determined by mass spectrometry that, in addition to cholesterol, the human hedgehog protein is palmitoylated. Peptide mapping and sequencing data indicate that the palmitoyl group is attached to the NH2 terminus of the protein on the alpha-amino group of Cys-24. Cell-free palmitoylation studies demonstrate that radioactive palmitic acid is readily incorporated into wild type Sonic hedgehog, but not into variant forms lacking the Cys-24 attachment site. The lipid-tethered forms of hedgehog showed about a 30-fold increase in potency over unmodified soluble hedgehog in a cell- based (C3H10T1/2 alkaline phosphatase induction) assay, suggesting that the lipid tether plays an important role in hedgehog function. The observation that an extracellular protein such as Shh is palmitoylated is highly unusual and further adds to the complex nature of this protein.
Improving the pharmacokinetics/pharmacodynamics of prolactin, GH, and their antagonists by fusion to a synthetic albumin-binding peptide (2009)

To prolong the circulation half-life of human prolactin (hPRL), human GH (hGH), and their competitive antagonists, hPRL-G129R and hGH-G120R, we examined the effects of fusing a serum albumin-binding peptide (SA20) to their amino- or carboxyl-terminus. Fusion of the SA20 peptide to the amino-terminus of the ligands was less detrimental upon their ability to induce or inhibit signal transduction and cell proliferation in vitro than fusion to the carboxyl-terminus. Pharmacokinetic (PK) studies in mice revealed that the half-life of SA20-hPRL and SA20-hGH was prolonged and their clearance was reduced in comparison with hPRL and hGH. Pharmacodynamic (PD) studies in 8-week-old female mice revealed that lobuloalveolar development in mammary glands was greater in all three groups (daily, every 2 days, or every third day over a 12-day period) of mice treated with SA20-hPRL (4 mg/kg) compared with hPRL (3.59 mg/kg). Similarly, daily administration (i.p.) of SA20-hGH (8 mg/kg) or hGH (7.15 mg/kg) to 23-day-old female mice over a 40-day period revealed the superiority of SA20-hGH over hGH as measured by weight gain, body length, and lobuloalveolar development in the mammary glands. These findings indicate that SA20 modification of hPRL, hGH, and their respective antagonists improves their PK/PD properties.
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model (2007)

Many potential treatments for Alzheimer's disease target amyloid-beta peptides (Abeta), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Abeta-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Abeta levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions.
A simplified architecture for module (2/sup n/+1) multiplication (1998)

The module (2/sup n/+1) multiplication is widely used in the computation of convolutions and in RNS arithmetic and, thus, it is important to reduce the calculation delay. This paper presents a concept of a module (2/sup n/+1) carry save adder (MCSA) and uses two MCSAs to perform the residue reduction. We also apply Booth's algorithm to the module (2/sup n/+1) multiplication scheme in order to reduce the number of partial products. With these techniques, the new architecture reduces the multiplier's calculation delay and is suitable for VLSI implementation for moderate and large n (n/spl ges/16).
Conductive Surface Modification with Aluminum of High Capacity Layered Li[Li0.2Mn0.54Ni0.13Co0.13]O2 Cathodes (2010)

The electrode films fabricated with the high capacity layered oxide Li[Li0.2Mn0.54Ni0.13Co0.13]O2 have been surface modified with metallic aluminum by a thermal evaporation process. The morphology and electrochemical performances of the bare and the Al-coated cathodes have been investigated by scanning electron microscopy (SEM) and charge−discharge measurements. Compared to the bare Li[Li0.2Mn0.54Ni0.13Co0.13]O2 cathode, the Al-coated cathodes (coating time ≤ 30 s) exhibit higher discharge capacity with lower irreversible capacity loss, better cyclability, and higher rate capability. Specifically, the 20 s Al-coated cathode exhibits the highest capacity (278 mAh/g at C/20 rate) and the best rate capability (157 mAh/g at 5C rate), while the 30 s Al-coated cathode displays the best cyclability (268 mAh/g with a capacity retention of 98% in 50 cycles). An analysis of the charge−discharge capacity values, surface conductivity evaluation, and electrochemical impedance spectroscopy (EIS) measurements reveal that the improved electrochemical performances are due to the suppression of both the oxygen vacancy elimination at the end of the first charge and side reactions with the electrolyte and the decrease in charge transfer polarization by the Al-modification layer.
Reduction of natural enones in the presence of cerium trichloride (1978)

The reduction of αβ-unsaturated ketones with sodium borohydride in methanol solution in the presence of cerium chloride gives almost exclusively the allylic alcohol, sometimes stereoselectively; the reduction of a variety of natural products containing a conjugated keto-group is described.
Human monoclonal antibody against ganglioside GD2: use in development of enzyme-linked immunosorbent assay for the monitoring of anti-GD2 in cancer patients. (1984)

Ganglioside GD2 is expressed on membranes of human melanoma cells and induces antibody responses in patients with melanoma. In this study a new enzyme-linked immunosorbent assay was developed for detection of human antibody against GD2. A human IgM monoclonal anti-GD2 antibody was used for development of the assay. The antigen, GD2, was prepared from human brain. Four micrograms of GD2 was required to coat a well in a polystyrene microtiter plate. As little as 10 ng of antibody could be detected. The applicability of the assay for detection of serum anti-GD2 antibody was demonstrated with sera from patients immunized with GD2-positive melanoma cell vaccine.
Improved Preservation of Saphenous Vein Grafts by the Use of Glyceryl Trinitrate–Verapamil Solution During Harvesting (1995)

First, pharmacological treatment of SV during harvesting, especially with GV solution, allows the use of a lower distension pressure and reduces the breakdown of high-energy phosphates in the vein wall. Second, topical and intraluminal use of GV solution during vein harvesting improves endothelial coverage compared with the topical use of Pap or no pharmacological treatment.
Regulation of Transforming Growth Factor β–Activated Kinase Activation by Epigallocatechin‐3‐Gallate in Rheumatoid Arthritis Synovial Fibroblasts: Suppression of K63‐Linked Autoubiquitination of Tumor Necrosis Factor Receptor–Associated Factor 6 (2015)

Our findings provide a rationale for targeting TAK1 for the treatment of RA with EGCG.
High-Level Extracellular Production of α-Cyclodextrin Glycosyltransferase with recombinant Escherichia coli BL21 (DE3) (2011)

High-level production of α-cyclodextrin glycosyltransferase (CGTase) is one of the key factors in α-cyclodextrin (CD) preparation. In the present study, a fed-batch fermentation strategy for high-cell-density cultivation of Escherichia coli and the extracellular production of recombinant α-CGTase from Paenibacillus macerans JFB05-01 was established. A combined feeding strategy based on both specific growth rate before induction and the amount of glycerol residues after induction was used to control cell growth, acetate production, and glycerol consumption. When induced by lactose, a feeding solution with complex nitrogen was found beneficial for α-CGTase production. In addition, different induction temperatures and induction points were investigated, and the results indicated that these factors played an important role in α-CGTase production. When induced at 25 °C and at a dry cell weight of 30 g L(-1), the extracellular activity of α-CGTase could reach 275.3 U mL(-1).
Hypophosphatasia (2007)

Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The prevalence of severe forms of the disease has been estimated at 1/100 000. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of teeth without bone symptoms. Depending on the age at diagnosis, six clinical forms are currently recognized: perinatal (lethal), perinatal benign, infantile, childhood, adult and odontohypophosphatasia. In the lethal perinatal form, the patients show markedly impaired mineralization in utero. In the prenatal benign form these symptoms are spontaneously improved. Clinical symptoms of the infantile form are respiratory complications, premature craniosynostosis, widespread demineralization and rachitic changes in the metaphyses. The childhood form is characterized by skeletal deformities, short stature, and waddling gait, and the adult form by stress fractures, thigh pain, chondrocalcinosis and marked osteoarthropathy. Odontohypophosphatasia is characterized by premature exfoliation of fully rooted primary teeth and/or severe dental caries, often not associated with abnormalities of the skeletal system. The disease is due to mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL; OMIM# 171760) encoding the tissue-nonspecific alkaline phosphatase (TNAP). The diagnosis is based on laboratory assays and DNA sequencing of the ALPL gene. Serum alkaline phosphatase (AP) activity is markedly reduced in hypophosphatasia, while urinary phosphoethanolamine (PEA) is increased. By using sequencing, approximately 95% of mutations are detected in severe (perinatal and infantile) hypophosphatasia. Genetic counseling of the disease is complicated by the variable inheritance pattern (autosomal dominant or autosomal recessive), the existence of the uncommon prenatal benign form, and by incomplete penetrance of the trait. Prenatal assessment of severe hypophosphatasia by mutation analysis of chorionic villus DNA is possible. There is no curative treatment for hypophosphatasia, but symptomatic treatments such as non-steroidal anti-inflammatory drugs or teriparatide have been shown to be of benefit. Enzyme replacement therapy will be certainly the most promising challenge of the next few years.
Video OCR for digital news archive (1998)

Video OCR is a technique that can greatly help to locate topics of interest in a large digital news video archive via the automatic extraction and reading of captions and annotations. News captions generally provide vital search information about the video being presented, the names of people and places or descriptions of objects. In this paper, two difficult problems of character recognition for videos are addressed: low resolution characters and extremely complex backgrounds. We apply an interpolation filter, multi-frame integration and a combination of four filters to solve these problems. Segmenting characters is done by a recognition-based segmentation method and intermediate character recognition results are used to improve the segmentation. The overall recognition results are good enough for use in news indexing. Performing video OCR on news video and combining its results with other video understanding techniques will improve the overall understanding of the news video content.
Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells (2006)

Newborns are prone to microbial infection and have poor memory responses to multiple antigens. We have previously shown that human neonatal blood monocytes exhibit impaired TNF-alpha responses to most known TLR agonists, including the pure TLR7 agonist imiquimod. Surprisingly, however, neonatal TNF-alpha responses to the imiquimod congener R-848 (TLR 7/8) were fully intact. We now show that TLR8 agonists, including R-848 (TLR7/8), the imidazoquinoline congeners 3M-003 (TLR7/8) and 3M-002 (TLR8), as well as single-stranded viral RNAs (TLR8) induced robust production of the Th1-polarizing cytokines TNF-alpha and IL-12 from neonatal antigen-presenting cells (APCs) that substantially exceeds responses induced by TLR-2, -4, or -7 (alone) agonists. TLR8 agonists also effectively induced up-regulation of the costimulatory molecule CD40 on neonatal and adult myeloid dendritic cells (DCs). The strong activity of TLR8 agonists correlates with their induction of p38 MAP kinase phosphorylation and with degradation of IkappaB-alpha in both neonatal and adult monocytes. We conclude that TLR8 agonists are uniquely efficacious in activating costimulatory responses in neonatal APCs and suggest that these agents are promising candidate adjuvants for enhancing immune responses in human newborns.
Early Introduction of Oral Feeding in Preterm Infants (2002)

Early introduction of oral feeding accelerates the transition time from tube to all oral feeding. This not only allows earlier attainment of all oral feeding, but it also provides practice opportunities that enhance the oral motor skills necessary for safe and successful feeding.
Parallel Evolutionary Multi-Objective Optimization on Large, Heterogeneous Clusters: An Applications Perspective (2008)

Real-world operational use of parallel multi-objective evolutionary algorithms requires successful searches in constrained wall-clock periods, limited trial-and-error algorithmic analysis, and scalable use of heterogeneous computing hardware. This study provides a cross-disciplinary collaborative effort to assess and adapt parallel multi-objective evolutionary algorithms for operational use in satellite constellation design using large dedicated clusters with heterogeneous processor speeds/architectures. A statistical, metric-based evaluation framework is used to demonstrate how time-continuation, asynchronous evolution, dynamic population sizing, and epsilon dominance archiving can be used to enhance both simple master–slave parallelization strategies and more complex multiple-population schemes. Results for a benchmark constellation design coverage problem show that simple master– slave schemes that exploit time-continuation are often sufficient and potentially superior to complex multiple-population schemes.
Antenna selection for MIMO-OFDM spatial multiplexing system (2003)

Transmit antenna selection is a promising closed-loop approach to introduce transmit-diversity for MIMO system. It offers performance improvement compared to the open loop schemes with equivalent complexity by only using low rate feedback link. Two categories of selection criteria were reported, which are capacity-oriented criteria (R. Blum, et al., 2002)and performance-oriented criteria (R.W. Heath, et al., 2001). In this paper, we focus on the later case. We present an analytical bound of transmit-diversity gain provided by antenna selection in flat fading channels. An antenna selection criterion is proposed for MIMO-OFDM in frequency selective fading channels.
Methylation of protein aspartates and deamidated asparagines as a function of blood bank storage and oxidative stress in human red blood cells (2018)

While methylation of basic amino acid residues serves as an epigenetic modification in nucleated cells, protein methylation at carboxylate side chains and deamidated asparagines is a nonepigenetic posttranslational sensor of oxidative stress and refrigerated storage in anucleated human RBCs.