gebhart/patrepeval huggingface dataset:
Metals in Medicine (2009)

Feature Boxes. Preface. Acknowledgments. 1 Inorganic Chemistry Basics. 1.1 Crystal field theory. 1.2 Molecular orbital theory. 1.3 Absorption spectra of metal complexes. 1.4 Magnetic properties of metal complexes. 1.5 Reactions of metal complexes. Problems. References. Further reading. 2 Metallo-Drugs and Their Action. 2.1 Introduction. 2.2 Proteins as targets for metallo-drugs. 2.3 DNA as a target for metallo-drugs. 2.4 Reaction of metal complexes in the biological milieu. 2.5 Evaluating the pharmacological effects of agents. 2.6 From discovery to the marketplace. Problems. References. Further reading. 3 Cisplatin. 3.1 Physical and chemical properties of cisplatin. 3.2 Formulation, administration and pharmacokinetics. 3.3 Reaction of cisplatin in biological media. 3.4 Uptake, cytotoxicity and resistance. 3.5 Interaction of cisplatin with cellular targets. Problems. References. Further reading. 4 Platinum Anticancer Drugs. 4.1 Carboplatin. 4.2 Oxaliplatin. 4.3 New platinum agents. Problems. References. Further reading. 5 Ruthenium, Titanium and Gallium for Treating Cancer. 5.1 Ruthenium compounds for treating cancer. 5.2 Titanium compounds for treating cancer. 5.3 Gallium for treating cancer. Problems. References. Further reading. 6 Gold Compounds for Treating Arthritis, Cancer and Other Diseases. 6.1 Chemistry of gold in biological media. 6.2 Gold compounds for treating arthritis. 6.3 Gold complexes for treating cancer. 6.4 Gold complexes for treating AIDS and other diseases. Problems. References. Further reading. 7 Vanadium, Copper and Zinc in Medicine. 7.1 Vanadium for treating diabetes. 7.2 Role of copper and other metal ions in Alzheimer's disease. 7.3 Copper in Wilson's and Menkes diseases. 7.4 Zinc-bicyclam: a chemokine receptor antagonist. Problems. References. Further reading. 8 Metal Complexes for Diagnosing Disease. 8.1 Technetium in diagnostic nuclear medicine. 8.2 Metal compounds as contrast agents for MRI. 8.3 Radionuclides for palliative care and cancer treatment. Problems. References. Further reading. 9 Nanomedicine. 9.1 Nanoscience for treating disease. 9.2 Nanomedicine in diagnosing disease. 9.3 Potential health risks of nanoparticles. Problems. References. Further reading. Index.
Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients (2012)

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.
Mesoporous TiO2: Comparison of Classical Sol−Gel and Nanoparticle Based Photoelectrodes for the Water Splitting Reaction (2010)

This paper describes a systematic comparison of the photoelectrochemical properties of mesoporous TiO(2) films prepared by the two most prevalent templating methods: The use of preformed, crystalline nanoparticles is generally considered advantageous compared to the usage of molecular precursors such as TiCl(4), since the latter requires a separate heat treatment at elevated temperature to induce crystallization. However, our photoelectrochemical experiments clearly show that sol-gel derived mesoporous TiO(2) films cause an about 10 times higher efficiency for the water splitting reaction than their counterparts obtained from crystalline TiO(2) nanoparticles. This result indicates that for electrochemical applications the performance of nanoparticle-based metal oxide films might suffer from insufficient electronic connectivity.
Imaging and energetics of single SSB-ssDNA molecules reveal intramolecular condensation and insight into RecOR function (2015)

Escherichia coli single-stranded DNA (ssDNA) binding protein (SSB) is the defining bacterial member of ssDNA binding proteins essential for DNA maintenance. SSB binds ssDNA with a variable footprint of ∼30-70 nucleotides, reflecting partial or full wrapping of ssDNA around a tetramer of SSB. We directly imaged single molecules of SSB-coated ssDNA using total internal reflection fluorescence (TIRF) microscopy and observed intramolecular condensation of nucleoprotein complexes exceeding expectations based on simple wrapping transitions. We further examined this unexpected property by single-molecule force spectroscopy using magnetic tweezers. In conditions favoring complete wrapping, SSB engages in long-range reversible intramolecular interactions resulting in condensation of the SSB-ssDNA complex. RecO and RecOR, which interact with SSB, further condensed the complex. Our data support the idea that RecOR--and possibly other SSB-interacting proteins-function(s) in part to alter long-range, macroscopic interactions between or throughout nucleoprotein complexes by microscopically altering wrapping and bridging distant sites.
Thymic lymphomas in interleukin 9 transgenic mice. (1994)

Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo. Although no major histological or morphological modifications of the lymphoid system were observed in most animals, approximately 7% of transgenic mice developed thymic lymphomas at the age of 3-9 months. The tumor cells, which were clonal, with unique T cell rearrangements, were double positive for the expression of CD4 and CD8. The need for additional transforming events, suggested by the low incidence of spontaneous tumors, was further indicated by the high susceptibility of the transgenic animals to injections of low doses of N-methyl-N-nitrosourea, a chemical carcinogen with a thymic tropism. Expression of interleukin 9 was required for optimal tumor growth in vivo, as one of the tumors studied, which had lost the transgene, was much more efficiently transplanted into transgenic than in normal mice. Moreover, the in vitro proliferative activity of interleukin 9 on cell lines derived from such transgene-negative tumors suggests that an autocrine loop mediates the proliferation of these cells in vivo. Taken together, these results indicate that dysregulated IL-9 expression could be involved in the development of some T cell malignancies.
Purification and characterization of an α-1,2-mannosidase involved in processing asparagine-linked oligosaccharides (1989)

A calcium-dependent alpha-1,2-mannosidase involved in the processing of asparagine-linked oligosaccharides was purified to homogeneity from rabbit liver microsomes. N-terminal amino acid analysis was consistent with the presence of a homogeneous protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under both reducing and nonreducing conditions, revealed a single protein band with an apparent molecular weight of 52,000. Gel filtration and sedimentation analysis under nondenaturing conditions suggested that the purified enzyme is a monomeric protein. The mannosidase is a glycoprotein based on the presence of protein-linked sugar and specific binding of the enzyme to concanavalin A-Sepharose. Purified mannosidase was optimally active between pH 5.0 and 6.0. The enzyme was inactive with p-nitrophenyl-alpha-D-mannopyranoside and was inhibited by deoxymannojirimycin but not by swainsonine. The enzyme was specifically activated by Ca2+, with half-maximal activation occurring at concentrations of 10 microM or less and was inhibited by Mn2+, Co2+, Ba2+, and Zn2+. Calcium ions protected the enzyme against inactivation by p-chloromercuribenzoate. Rabbit liver mannosidase hydrolyzed alpha-1,2-mannosyl-mannose linkages in a variety of substrates including methyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (Schutzbach, J. S. (1987) Anal. Biochem. 167, 279-283), ovalbumin glycopeptide IV, and the high mannose chains of thyroglobulin and phytohemagglutinin-P. Approximately 70% of the alpha-1,2-linked mannosyl units in the oligosaccharides of thyroglobulin were accessible to rabbit liver alpha-mannosidase, whereas most of the alpha-1,2-mannosyl units in phytohemagglutinin were resistant to digestion prior to heat denaturation of the plant lectin.
Novel cardiolipin therapeutic protects endothelial mitochondria during renal ischemia and mitigates microvascular rarefaction, inflammation, and fibrosis (2014)

Microvascular rarefaction, or loss of microvascular density, is increasingly implicated in the progression from acute ischemic kidney injury to chronic kidney disease. Microvascular dropout results in chronic tissue hypoxia, interstitial inflammation, and fibrosis. There is currently no therapeutic intervention for microvascular rarefaction. We hypothesize that capillary dropout begins with ischemic damage to endothelial mitochondria due to cardiolipin peroxidation, resulting in loss of cristae and the failure to regenerate ATP upon reperfusion. SS-31 is a cell-permeable peptide that targets the inner mitochondrial membrane and binds selectively to cardiolipin. It was recently shown to inhibit cardiolipin peroxidation by cytochrome c peroxidase activity, and it has been shown to protect mitochondrial cristae in proximal tubular cells during ischemia, and accelerated ATP recovery upon reperfusion. We found mitochondrial swelling and loss of cristae membranes in endothelial and medullary tubular epithelial cells after 45-min ischemia in the rat. The loss of cristae membranes limited the ability of these cells to regenerate ATP upon reperfusion and led to loss of vascular integrity and to tubular cell swelling. SS-31 prevented mitochondria swelling and protected cristae membranes in both endothelial and epithelial cells. By minimizing endothelial and epithelial cell injury, SS-31 prevented "no-reflow" after ischemia and significantly reduced the loss of peritubular capillaries and cortical arterioles, interstitial inflammation, and fibrosis at 4 wk after ischemia. These results suggest that mitochondria protection represents an upstream target for pharmacological intervention in microvascular rarefaction and fibrosis.
Classicality of the order parameter during a phase transition (2000)

We analyze the quantum to classical transition of the order parameter in second order phase transitions. We consider several toy models in nonrelativistic quantum mechanics. We study the dynamical evolution of a wave packet initially peaked around a local maximum of the potential using variational approximations and also exact numerical results. The influence of the environment on the evolution of the density matrix and the Wigner function is analyzed in great detail. We also discuss the relevance of our results to the analysis of phase transitions in field theory. In particular, we argue that previous results about the classicality of the order parameter in $O(N)$ models may be a consequence of the large N approximation.
Synthesis and spectroscopic properties of a new 4-bora-3a,4a-diaza-s-indacene (BODIPY®) dye (1999)

The constrained dye 3 was prepared and shown to have a sharper, red-shifted, and more intense fluorescence emission than the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY®) dye 2 in which the aryl groups can rotate freely.
[Drug and gene delivery using electrotransfer]. (2001)

The use of a low intensity current (iontophoresis) and high voltage pulses (electroporation which permeabilizes lipid bilayers) has a potential for the administration of conventional and biotechnology-produced drugs. Iontophoresis and electroporation enhance transdermal delivery of drugs, including peptides and oligonucleotides. Electrochemotherapy, i.e., combination of a systemic or local delivery of a non-permeant cytostatic drug with electroporation, kills locally tumor cells. Recently, it has been shown that the local injection of a plasmid before electroporation increases significantly gene transfection. Hence, electrotransfer is a promising alternative for drug and gene delivery.
Stimulation of Open Complex Formation by Nicks and Apurinic Sites Suggests a Role for Nucleation of DNA Melting in Escherichia coli Promoter Function (1998)

We report the effects of depurination and prenicking at various positions of the phage lambda prmup-1Delta265 promoter DNA on the rate of open complex formation. We have found that depurination and prenicking at positions around the -10 region strongly stimulated the rate of open complex formation. Since nicking and depurination are known to destabilize DNA helical structure, our observations indicate that the instability of the -10 region is important for open complex formation. We further infer that (i) the nucleation of DNA melting, which occurs during the isomerization from the closed complex into the open complex, contributes to the rate of open complex formation; (ii) the nucleation of melting occurs around the -10 region; and (iii) the propagation of DNA melting from the nucleation region is not rate-limiting. In addition, we have found that depurination at several positions inhibited open complex formation. We used dimethyl sulfate modification protection studies to show that most of the guanine bases that are among these positions are in contact with RNA polymerase in the open complex.
Cooperative Regulation by Rac and Rho of Agrin-induced Acetylcholine Receptor Clustering in Muscle Cells (2003)

A key aspect of neuromuscular synapse formation is the clustering of muscle acetylcholine receptors (AChR) at synaptic sites in response to neurally secreted agrin. Agrin-induced AChR clustering in cultured myotubes proceeds via the initial formation of small microclusters, which then aggregate to form AChR clusters. Here we show that the coupling of agrin signaling to AChR clustering is dependent on the coordinated activities of Rac and Rho GTPases. The addition of agrin induces the sequential activation of Rac and Rho in C2 muscle cells. The activation of Rac is rapid and transient and constitutes a prerequisite for the subsequent activation of Rho. This temporal pattern of agrin-induced Rac and Rho activation reflects their respective roles in AChR cluster formation. Whereas agrin-induced activation of Rac is necessary for the initial phase of AChR cluster formation, which involves the aggregation of diffuse AChR into microclusters, Rho activation is crucial for the subsequent condensation of these microclusters into full-size AChR clusters. Co-expression of constitutively active forms of Rac and Rho is sufficient to induce the formation of mature AChR clusters in the absence of agrin. These results establish that Rac and Rho play distinct but complementary roles in the mechanism of agrin-induced AChR clustering.
Role of osteopontin in cellular signaling and metastatic phenotype (2008)

Osteopontin (opn) is a glyco-phosphoprotein that is expressed and secreted by numerous human cancers. Opn has pivotal role in cell adhesion, chemotaxis, prevention of apoptosis, invasion, migration and anchorage-independent growth of tumor cells. Extensive research has demonstrated the pivotal role of opn in regulation of cellular signaling, which controls neoplastic and malignant transformation. The elevated expression of opn has been observed in a variety of cancers. Recently, substantial evidence has linked opn with tumor metastasis and poor prognosis. However, the understanding of the molecular mechanisms that define the role of opn in cell invasion and metastasis is incomplete. The following review will discuss the molecular structure of opn, its function role in tumor cell metastasis and its downstream target genes that activate invasive mechanisms. Understanding of the role of opn in neoplastic transformation and its cellular target genes may enable development of novel anti-cancer therapy approaches.
Surface microstructuring and long-range ordering of silicon nanoparticles (2002)

Pulsed-laser irradiation was used to induce the formation of linear arrays of nanoparticles that can extend over millimeter distances. On flat surfaces, the irradiation induces the fragmentation and clustering of a thin silicon film pulsed-laser deposited on silicon into nanoparticles that grow to 30–40 nm in diameter. The nanoparticles aggregate into clusters that migrate, forming short curvilinear groups that exhibit a short-range ordering. If a region containing a microscopic roughness is introduced, the nanoparticles are forced to align into long and remarkably straight lines with line spacing very close to the laser wavelength. A close connection is established between the nanoparticle alignment and the evolution of laser-induced periodic surface structures. The microscopic roughness solely serves as a trigger to produce the alignment.
Citrus Soil pH Management (2019)

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Management of both soil pH and nutrients is required to maintain soil fertility levels and ensure economic agricultural production. Maintaining soil in the 6.0-6.5 pH range is best for most crops including citrus. This new two-page publication of the UF/IFAS Department of Soil and Water Sciences, written by Kelly Morgan, explains the effects of soil pH on citrus as well as options for management.https://edis.ifas.ufl.edu/ss666&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;
Activation of coagulation releases endothelial cell mitogens. (1986)

Recent studies have indicated that endothelial cell function includes elaboration of growth factors and regulation of coagulation. In this paper we demonstrate that activated coagulation Factor X (Factor Xa), a product of the coagulation mechanism generated before thrombin, induces enhanced release of endothelial cell mitogens, linking these two functions. Mitogenic activity generated by cultured bovine aortic endothelial cells in response to Factor Xa included platelet-derived growth-factor-like molecules based on a radioreceptor assay. Effective induction of mitogens by Factor Xa required the integrity of the enzyme's active center and the presence of the gamma-carboxyglutamic acid-containing domain of the molecule. Factor Xa-induced release of mitogens from endothelium occurred in serum-free medium and was not altered by hirudin or antibody to Factor V, indicating that it was a direct effect of Factor Xa and was not mediated by thrombin. Elaboration of mitogenic activity required only brief contact between Factor Xa and endothelium, and occurred in a time-dependent manner. Generation of enhanced mitogenic activity in response to Factor Xa was unaffected by the presence of actinomycin D and was not associated with increased hybridization of RNA from treated cells to a v-sis probe. Release of mitogenic activity was dependent on the dose of Factor Xa, being half-maximal at 0.5 nM and reaching a maximum by 5 nM. Radioligand binding studies demonstrated a class of endothelial cell sites half-maximally occupied at a Factor Xa concentration of 0.8 nM. The close correspondence between the parameters of Factor Xa-induced mitogen release and Factor Xa binding suggests these sites may be related. When Factor X was activated on the endothelial cell surface by Factors IXa and VIII, the Factor Xa formed resulted in the induction of enhanced release of mitogenic activity. These data suggest a mechanism by which the coagulation system can locally regulate endothelial cell function and vessel wall biology before thrombin-induced release of growth factors from platelets.
Pulsed Carbon Dioxide Laser Resurfacing of Photoaged Facial Skin (1996)

Resurfacing of photoaged skin by means of a high-energy, microsecond-domain pulsed CO2 laser with a specific clinical treatment protocol results in predictable improvement in perioral and periorbital wrinkling and photodamage with minimal risks. Heat-induced collagen shrinkage appears to contribute to these results by tightening loose skin and folds.
Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors (1997)

One hope to maintain the benefits of antiviral therapy against the human immunodeficiency virus type 1 (HIV-1), despite the development of resistance, is the possibility that resistant variants will show decreased viral fitness. To study this possibility, HIV-1 variants showing high-level resistance (up to 1,500-fold) to the substrate analog protease inhibitors BILA 1906 BS and BILA 2185 BS have been characterized. Active-site mutations V32I and I84V/A were consistently observed in the protease of highly resistant viruses, along with up to six other mutations. In vitro studies with recombinant mutant proteases demonstrated that these mutations resulted in up to 10(4)-fold increases in the Ki values toward BILA 1906 BS and BILA 2185 BS and a concomitant 2,200-fold decrease in catalytic efficiency of the enzymes toward a synthetic substrate. When introduced into viral molecular clones, the protease mutations impaired polyprotein processing, consistent with a decrease in enzyme activity in virions. Despite these observations, however, most mutations had little effect on viral replication except when the active-site mutations V32I and I84V/A were coexpressed in the protease. The latter combinations not only conferred a significant growth reduction of viral clones on peripheral blood mononuclear cells but also caused the complete disappearance of mutated clones when cocultured with wild-type virus on T-cell lines. Furthermore, the double nucleotide mutation I84A rapidly reverted to I84V upon drug removal, confirming its impact on viral fitness. Therefore, high-level resistance to protease inhibitors can be associated with impaired viral fitness, suggesting that antiviral therapies with such inhibitors may maintain some clinical benefits.
Exon skipping and translation in patients with frameshift deletions in the dystrophin gene. (1993)

Although many Duchenne muscular dystrophy patients have a deletion in the dystrophin gene which disrupts the translational reading frame, they express dystrophin in a small proportion of skeletal muscle fibers ("revertant fibers"). Antibody studies have shown, indirectly, that dystrophin synthesis in revertant fibers is facilitated by a frame-restoring mechanism; in the present study, the feasibility of mRNA splicing was investigated. Dystrophin transcripts were analyzed in skeletal muscle from individuals possessing revertant fibers and a frameshift deletion in the dystrophin gene. In each case a minor in-frame transcript was detected, in which exons adjacent to those deleted from the genome had been skipped. There appeared to be some correlation between the levels of in-frame transcripts and the predicted translation products. Low levels of alternatively spliced transcripts were also present in normal muscle. The results provide further evidence of exon skipping in the dystrophin gene and indicate that this may be involved in the synthesis of dystrophin by revertant fibers.