gebhart/patrepeval huggingface dataset:
Purification and structure of the intact Ada regulatory protein of Escherichia coli K12, O6-methylguanine-DNA methyltransferase. (1985)

The ada gene of Escherichia coli K12, the regulatory gene for the adaptive response of bacteria to alkylating agents, was cloned and placed under the control of the lac regulatory region on a multicopy runaway plasmid, thereby yielding a hybrid plasmid pYN3059. Ada protein with a molecular weight of about 38,000 was overproduced when cells harboring pYN3059 were incubated at 42 degrees C in the presence of a lac inducer, isopropyl-beta-D-thiogalactoside. Taking advantage of overproduction of Ada protein, we purified the protein to apparent physical homogeneity. The purified 38,000-dalton Ada protein transferred the methyl group from the O6-methylguanine residue of alkylated DNA to the Ada protein, per se. Although the Ada protein was degraded to smaller polypeptides when crude extracts or partially purified preparations were incubated in a high ionic-strength buffer at neutral pH, the purified Ada protein remained stable under the same conditions, indicating that the Ada protein may not undergo autodegradation. An amino-terminal sequence and total amino acid composition of the purified Ada protein were in accord with nucleotide sequence of the ada gene, determined by the dideoxy method using M13 phage. It was deduced that Ada protein comprises 354 amino acids and its molecular weight is 39,385. The promoter for the ada gene was determined by S1 nuclease mapping.
A Robust Platform for the Synthesis of New Tetracycline Antibiotics (2008)

Tetracyclines and tetracycline analogues are prepared by a convergent, single-step Michael-Claisen condensation of AB precursor 1 or 2 with D-ring precursors of wide structural variability, followed by removal of protective groups (typically in two steps). A number of procedural variants of the key C-ring-forming reaction are illustrated in multiple examples. These include stepwise deprotonation of a D-ring precursor followed by addition of 1 or 2, in situ deprotonation of a D-ring precursor in mixture with 1 or 2, and in situ lithium-halogen exchange of a benzylic bromide D-ring precursor in the presence of 1 or 2, followed by warming. The AB plus D strategy for tetracycline synthesis by C-ring construction is shown to be robust across a range of different carbocyclic and heterocyclic D-ring precursors, proceeding reliably and with a high degree of stereochemical control. Evidence suggests that Michael addition of the benzylic anion derived from a given D-ring precursor to enones 1 or 2 is quite rapid at -78 degrees C, while Claisen cyclization of the enolate produced is rate-determining, typically occurring upon warming to 0 degrees C. The AB plus D coupling strategy is also shown to be useful for the construction of tetracycline precursors that are diversifiable by latter-stage transformations, subsequent to cyclization to form the C ring. Results of antibacterial assays and preliminary data obtained from a murine septicemia model show that many of the novel tetracyclines synthesized have potent antibiotic activities, both in bacterial cell culture and in vivo. The platform for tetracycline synthesis described gives access to a broad range of molecules that would be inaccessible by semisynthetic methods (presently the only means of tetracycline production) and provides a powerful engine for the discovery and, perhaps, development of new tetracycline antibiotics.
Soy isoflavonoid equol modulates the growth of benign and malignant prostatic epithelial cells in vitro (2002)

Equol is a biologically active metabolite of daidzein that has potent antiproliferative effects on benign and malignant prostatic epithelial cells at concentrations that can be obtained naturally through dietary soy consumption.
Intravascular and Mucosal Immunoglobulin A: Two Separate but Related Systems of Immune Defense? (1987)

Immunoglobulin A has long been referred to as the antibody of mucosal secretions. However, in the last few years there has been increased interest in serum IgA, in factors that regulate the various forms of IgA produced, and in the relationship between serum and mucosal IgA. Recent data indicate that in humans, the mucosal surfaces are neither the source nor the destination of serum IgA. By estimating the amounts of IgA produced at various sites throughout the body, we have shown that in humans more IgA is synthesized and secreted each day than IgG and IgM combined; about one third of this IgA is secreted directly into the vascular compartment and never reaches the mucosal surfaces. We also consider a possible role for serum IgA as the "discreet housekeeper," the relationship between cells that produce IgA in the serum and IgA in secretions, and factors that influence the various forms of IgA produced.
Serum Adiponectin Concentrations and Tissue Expression of Adiponectin Receptors Are Reduced in Patients with Prostate Cancer: A Case Control Study (2007)

Higher serum adiponectin is associated with a marked reduction in risk of prostate cancer, but not BPH, independently of other risk factors. Malignant prostate tissue samples have reduced expression of adiponectin receptors as compared with benign prostate tissue. These results support a role for adiponectin in the pathogenesis of prostate cancer.
Sliding-induced adhesion of stiff polymer microfibre arrays. II. Microscale behaviour (2008)

The adhesive pads of geckos provide control of normal adhesive force by controlling the applied shear force. This frictional adhesion effect is one of the key principles used for rapid detachment in animals running up vertical surfaces. We developed polypropylene microfibre arrays composed of vertical, 0.3 microm radius fibres with elastic modulus of 1 GPa which show this effect for the first time using a stiff polymer. In the absence of shear forces, these fibres show minimal normal adhesion. However, sliding parallel to the substrate with a spherical probe produces a frictional adhesion effect which is not seen in the flat control. A cantilever model for the fibres and the spherical probe indicates a strong dependence on the initial fibre angle. A novel feature of the microfibre arrays is that adhesion improves with use. Repeated shearing of fibres temporarily increases maximum shear and pull-off forces.
MIDDLE CEREBRAL ARTERY STENTING FOR ACUTE ISCHEMIC STROKE AFTER UNSUCCESSFUL MERCI RETRIEVAL (2007)

Angiographic recanalization has been associated with improvement in clinical outcome after acute cerebral ischemia. Recanalization is not always achieved using the Merci retriever. We found that stenting after unsuccessful Merci retrieval resulted in a high rate of angiographic success. Further research into refining indications and optimizing outcome is warranted.
Development of “substrate-trapping” mutants to identify physiological substrates of protein tyrosine phosphatases (1997)

The identification of substrates of protein tyrosine phosphatases (PTPs) is an essential step toward a complete understanding of the physiological function of members of this enzyme family. PTPs are defined by a conserved catalytic domain harboring 27 invariant residues. From a mutagenesis study of these invariant residues that was guided by our knowledge of the crystal structure of PTP1B, we have discovered a mutation of the invariant catalytic acid (Asp-181 in PTP1B) that converts an extremely active enzyme into a "substrate trap." Expression of this D181A mutant of PTP1B in COS and 293 cells results in an enzyme that competes with endogenous PTP1B for substrates and promotes the accumulation of phosphotyrosine primarily on the epidermal growth factor (EGF) receptor as well as on proteins of 120, 80, and 70 kDa. The association between the D181A mutant of PTP1B and these substrates was sufficiently stable to allow isolation of the complex by immunoprecipitation. As predicted for an interaction between the substrate-binding site of PTP1B and its substrates, the complex is disrupted by vanadate and, for the EGF receptor, the interaction absolutely requires receptor autophosphorylation. Furthermore, from immunofluorescence studies, the D181A mutant of PTP1B appeared to retain the endogenous EGF receptor in an intracellular complex. These results suggest that the EGF receptor is a bona fide substrate for PTP1B in vivo and that one important function of PTP1B is to prevent the inappropriate, ligand-independent, activation of newly synthesized EGF receptor in the endoplasmic reticulum. This essential catalytic aspartate residue is present in all PTPs and has structurally equivalent counterparts in the dual-specificity phosphatases and the low molecular weight PTPs. Therefore we anticipate that this method may be widely applicable to facilitate the identification of substrates of other members of this enzyme family.
Immune surveillance against a solid tumor fails because of immunological ignorance (1999)

Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, overall immune surveillance against such tumors seems relatively inefficient. We studied immune surveillance against a s.c. sarcoma expressing a characterized viral tumor antigen. Surprisingly, the tumor cells were capable of inducing a protective cytotoxic T cell response if transferred as a single-cell suspension. However, if they were transplanted as small tumor pieces, tumors readily grew. Tumor growth correlated strictly with (i) failure of tumor cells to reach the draining lymph nodes and (ii) absence of primed cytotoxic T cells. Cytotoxic T cells were not tolerant or deleted because a tumor antigen-specific cytotoxic T cell response was readily induced in lymphoid tissue by immunization with virus or with tumor cells even in the presence of large tumors. Established tumors were rejected by vaccine-induced effector T cells if effector T cells were maintained by prolonged or repetitive vaccination, but not by single-dose vaccination. Thus, in addition to several other tumor-promoting parameters, some antigenic peripheral sarcomas-and probably carcinomas-may grow not because they anergize or tolerize tumor-specific T cells, but because such tumors are immunologically dealt with as if they were in a so-called immunologically privileged site and are ignored for too long.
Improved Electrical Conductivity of Graphene Films Integrated with Metal Nanowires (2012)

Polycrystalline graphene grown by chemical vapor deposition (CVD) on metals and transferred onto arbitrary substrates has line defects and disruptions such as wrinkles, ripples, and folding that adversely affect graphene transport properties through the scattering of the charge carriers. It is found that graphene assembled with metal nanowires (NWs) dramatically decreases the resistance of graphene films. Graphene/NW films with a sheet resistance comparable to that of the intrinsic resistance of graphene have been obtained and tested as a transparent electrode replacing indium tin oxide films in electrochromic (EC) devices. The successful integration of such graphene/NW films into EC devices demonstrates their potential for a wide range of optoelectronic device applications.
Oligosaccharides accumulated in the bovineβ‐mannosidosis kidney (1991)

The phenotype of bovine beta-mannosidosis (beta-mannosidase deficiency), recently identified in Salers cattle, is similar to the caprine form of the disease (Abbitt et al., 1991). This investigation was designed to characterize accumulated kidney oligosaccharides in bovine beta-mannosidosis. Oligosaccharides were extracted from the kidney of an affected Salers calf and purified by chromatographic techniques. The amount of accumulating oligosaccharides in 1 g of wet tissue was about 21 mumol. Structures of derivatized oligosaccharides were characterized by high-performance liquid chromatography, mass spectrometry, methylation analysis and sequential exoglycosidase digestions. The major accumulating oligosaccharides were Man beta 1-4GlcNAc and Man beta 1-4GlcNAc beta 1-4GlcNAc. Oligosaccharides accumulating in minor amounts were Man beta 1-4GlcNAc beta 1-4Man beta 1-4GlcNAc, Man alpha 1-6Man beta 1-4GlcNAc beta 1-4GlcNAc and Man beta 1-4GlcNAc beta 1-4Man beta 1-4GlcNAc beta 1-4GlcNAc. As in caprine beta-mannosidosis, oligosaccharides with terminal beta-mannose residues and cleaved as well as uncleaved chitobiose linkages were identified in bovine beta-mannosidosis kidney. The accumulating oligosaccharides in tissue were thus identical in bovine and caprine beta-mannosidosis; however, the source of the novel oligosaccharides remains to be determined.
Topology of receptor binding domains of mouse IFN- gamma . (1990)

IFN-gamma is an essential immunoregulatory lymphokine for a variety of immunologic functions including upregulation of MHC Ag. The elucidation of the structure, particularly the receptor binding domains, should further enhance our understanding of its mechanism of action, and provide a rational basis for modulation of its activity by alteration of its structure. A predicted model of murine IFN-gamma structure has been constructed based on data derived from our synthetic peptide studies, circular dichroism spectra, and predictive algorithms for secondary structure, surface accessibility, and tertiary structure, as well as predicted structural similarities to IL-2. Direct synthetic peptide competition studies using five overlapping peptides that encompassed the entire IFN-gamma sequence of 133 amino acids showed that only the N-terminus of IFN-gamma, IFN-gamma(1-39), blocked binding to receptor, suggesting that the N-terminus is directly involved in receptor binding. Rabbit antibodies to the N-terminal (IFN-gamma(1-39)) and C-terminal (IFN-gamma(95-133)) peptides neutralized IFN-gamma activity, whereas antibodies to the three peptides that spanned the internal region, sequence 36-107, were without effect. Thus, the antibody data support the involvement of the N-terminus as a receptor binding domain and also suggest that the C-terminus of the molecule is also a binding domain. Predictive algorithms assign six alpha-helices and five turns to the molecule and circular dichroism spectra of both intact human and murine IFN-gamma and synthetic peptides of murine IFN-gamma showed that the molecule is mainly alpha-helical in structure. Drawing mainly on the four alpha-helix bundle model, a common motif in globular proteins such as IFN-gamma and IL-2 (whose crystalline structure is known), we constructed a simple model of the tertiary structure of IFN-gamma that fits well with our synthetic peptide and circular dichroism data. The model consists of the four-alpha-helical bundle along with N- and C-terminal helices that are predicted to be closely associated and together form the receptor binding domains. The model presented should contribute to further understanding the molecular basis of IFN-gamma action and allow us to begin modulating the function of IFN-gamma through the design of agonists and antagonists.
Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease (2012)

Parkinson disease (PD) is a neurodegenerative disorder particularly characterized by the loss of dopaminergic neurons in the substantia nigra. Pesticide exposure has been associated with PD occurrence, and we previously reported that the fungicide benomyl interferes with several cellular processes potentially relevant to PD pathogenesis. Here we propose that benomyl, via its bioactivated thiocarbamate sulfoxide metabolite, inhibits aldehyde dehydrogenase (ALDH), leading to accumulation of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), preferential degeneration of dopaminergic neurons, and development of PD. This hypothesis is supported by multiple lines of evidence. (i) We previously showed in mice the metabolism of benomyl to S-methyl N-butylthiocarbamate sulfoxide, which inhibits ALDH at nanomolar levels. We report here that benomyl exposure in primary mesencephalic neurons (ii) inhibits ALDH and (iii) alters dopamine homeostasis. It induces selective dopaminergic neuronal damage (iv) in vitro in primary mesencephalic cultures and (v) in vivo in a zebrafish system. (vi) In vitro cell loss was attenuated by reducing DOPAL formation. (vii) In our epidemiology study, higher exposure to benomyl was associated with increased PD risk. This ALDH model for PD etiology may help explain the selective vulnerability of dopaminergic neurons in PD and provide a potential mechanism through which environmental toxicants contribute to PD pathogenesis.
Hot Electron Generation in Aqueous Solution at Oxide-Covered Tantalum Electrodes. Reduction of Methylpyridinium and Electrogenerated Chemiluminescence of Ru(bpy)32+ (1999)

We describe the injection of hot electrons into an aqueous solution by use of a Ta/Ta2O5 electrode. Evidence for this process was obtained by studying the chemically irreversible reduction of N-methylpyridinium ion (NMP+, E° = −1.37 V vs SHE). The reduction of NMP+ gives rise to a radical which undergoes rapid dimerization to produce a water-insoluble species, 1,1-tetrahydrobipyridine (TBP), that deposits on the electrode surface. The deposit was analyzed by AFM, XPS, IR-reflectance, and TOF/SIMS to provide evidence of TBP formation. We also investigated the electrochemical reduction of Ru(bpy)32+ to confirm the generation of hot electrons on a Ta/Ta2O5 electrode in water. The electrochemical and spectroelectrochemical results present a well-defined reduction wave at high overpotential on Ta/Ta2O5 which is not observed on Pt or Au electrodes. Reduction of Ru(bpy)33+ at a Ta/Ta2O5 electrode produces emission (electrogenerated chemiluminescence) and provides additional evidence of hot electron injection.
The Origins of Cellular Life (2010)

Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of functional information. Recent studies of vesicles composed of fatty-acid membranes have shed considerable light on pathways for protocell growth and division, as well as means by which protocells could take up nutrients from their environment. Additional work with genetic polymers has provided insight into the potential for chemical genome replication and compatibility with membrane encapsulation. The integration of a dynamic fatty-acid compartment with robust, generalized genetic polymer replication would yield a laboratory model of a protocell with the potential for classical Darwinian biological evolution, and may help to evaluate potential pathways for the emergence of life on the early Earth. Here we discuss efforts to devise such an integrated protocell model.
Inhibition of plant cell proteolytic activities that degrade tubulin (1985)

The requirement for proteinase inhibitors during the chromatographic isolation of tubulin from cultured cells of rose (Rosa sp. cv. Paul's scarlet) was examined by NadodecylSO4-polyacrylamide gel electrophoresis, electron microscopy and immunoblotting. Tubulin fractions isolated in the absence of proteinase inhibitors showed substoichiometric ratios of alpha-subunit to beta-subunit, and low molecular weight polypeptides, one (approximately 32 Kd) of which coassembled with polymers. Electron microscopy revealed polymorphic structures, including C- and S-shaped ribbons and free protofilaments. Immunoblotting experiments with IgGs to the individual alpha- and beta-subunits showed that some of the low molecular weight polypeptides were fragments of proteolytically degraded subunits. The use of low micromolar concentrations of the synthetic proteinase inhibitors leupeptin hemisulfate and pepstatin A protected tubulin from endogenous proteolytic activities during the isolation procedure and resulted in increased tubulin purity.
Peak to average power ratio reduction for OFDM systems with low complexity (2010)

Orthogonal frequency division multiplexing (OFDM) has gained popularity as a standard for various high data rate wireless communication systems due to the spectral bandwidth efficiency, robustness to frequency selective fading channels, etc. However, its high peak-to-average power ratio (PAPR) causes significant in-band distortion and high out-of-band radiation when it passes through a nonlinear device such as a high power amplifier (HPA). This paper reviews the main PAPR reduction schemes and introduces their modifications for achieving low-complexity required for practical implementation in wireless communication systems.
[The pharmacokinetics of a transdermal preparation of artesunate in mice and rabbits]. (1989)

Qinghaosu, also known as artemisinin and arteannuin, is a new type of antimalarial drug isolated from Artemisa annua L. Its low solubility in water and oil limited its widespread clinical use. Artesunate (sodium dihydroqinghaosu hydrogen hemisuccinate monoester) is easily soluble in water and is used iv in the treatment of acute cerebral and malignant malaria. However, artesunate was shown to have a very short half-life when given iv in animals as well as in human beings. A transdermal dosage form of artesunic acid had been prepared and was reported to have reliable suppressing and killing effects on plasmobium berghei in mice. This paper reports results of pharmacokinetic studies of this preparation when applied onto a fixed area of the shaved skin of mice and rabbits. Serum concentration of the drug was determined by a method of radioimmunoassay. The drug was found to be easily absorbed from the skin. The serum concentration-time curve is depicted in figures 1. Peak concentration of 1.8 micrograms/ml was reached at about 2 h when a dose of 25 mg/kg was given to rabbits. For mice, peak serum concentrations of 2.05 and 7.11 micrograms/ml were attained in about 0.5 h after doses of 31.3 and 71.4 mg/kg, respectively, while at a dose of 6.7 mg/kg a peak level of 0.82 micrograms/ml (a concentration more than 5000 times the IC50 of artesunate in in vitro tests on plasmodium berghei for antimalarial activity) was attained at about 4 h after application of the drug. The half-lives of the drug were found to be more than 2 h for both mice and rabbits.