gebhart/patrepeval huggingface dataset:
The Synthesis and Enzymatic Polymerization of Nucleotides Containing Mercury: Potential Tools for Nucleic Acid Sequencing and Structural Analysis (1973)

A simple acetoxymercuration reaction for introducing covalently bound mercury atoms into nucleotides is described. The 5-mercuriacetate derivatives of UTP, CTP, dUTP, and dCTP, as well as the 7-mercuriacetate derivative of 7-deazaATP, have been prepared by this procedure and tested as substrates for nucleic acid polymerases. These nucleotides, in the absence of added mercaptan, are not polymerized and in most instances are potent enzyme inhibitors. However, conversion of these mercuriacetates to mercurithio compounds in situ by the addition of one of various mercaptans, yields nucleoside triphosphates that are excellent substrates for all polymerases tested: Escherichia coli and T7 RNA polymerases, DNA polymerase I of E. coli, DNA polymerase of avian myeloblastosis virus, and calf-thymus terminal deoxynucleotidyl transferase. By varying the mercaptan used to promote syntheses it is possible to access certain structural limitations in the enzyme's nucleoside triphosphate binding site. These mercurinucleotides appear to have a diversity of potential applications: (1) as heavy-atom reagents for crystallographic and microscopic studies; (2) as affinity probes for enzymes sensitive to sulfhydryl modification; (3) as steric probes of substrate-binding sites on enzymes; and (4) as reagents for forming covalent protein-polynucleotide complexes.
Metallic resistively coupled single-electron transistor (1999)

We have fabricated and measured transport properties of resistively coupled single-electron transistors (R-SETs). In our version, a chromium thin-film resistive strip served as a gate and was connected directly to a mesoscopic island formed between two ultrasmall Al/AlOx/Al tunnel junctions. In current–voltage-gate voltage dependences of the R-SETs, a characteristic Coulomb blockade pattern was observed. Our simulations based on the orthodox theory of single-electron tunneling are in good qualitative agreement with the experimental data and indicate excessive electron temperature of the devices.
Mini ReviewFLT3: Receptor and Ligand (2004)

FLT3 is a receptor tyrosine kinase (RTK) expressed by immature hematopoietic progenitor cells. The ligand for FLT3 is a transmembrane or soluble protein and is expressed by a variety of cells including hematopoietic and marrow stromal cells; in combination with other growth factors, the ligand stimulates proliferation and development of stem cells, myeloid and lymphoid progenitor cells, dendritic cells and natural killer cells. Activation of the receptor leads to tyrosine phosphorylation of various key adaptor proteins known to be involved in different signal transduction pathways that control proliferation, survival and other processes in hematopoietic cells. FLT3 is not only of utmost interest regarding physiological processes of hematopoietic cells but also with regard to pathological aspects, namely leukemogenesis and diagnosis, prognosis and therapy of leukemia. Activating mutations of the receptor have been recognized as the most common genetic abnormality in acute myeloid leukemia (AML), occurring in about 30% of adult cases. AML patients with FLT3 mutations tend to have a poor prognosis, thus FLT3 is an attractive target of therapy, for instance using kinase inhibitors.
Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide. (2001)

Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompanied by induction of jun kinase activity and a marked increase in endogenous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhibitory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents.
Comparison of protein mixtures in aqueous humor by membrane preconcentration ‐ capillary electrophoresis ‐ mass spectrometry (1998)

The significance of proteomic research is coupled with the recent exponential growth of these investigations. Currently, the most popular techniques used for these studies include the coupling of 1- and 2-dimensional electrophoresis with mass spectrometric analysis of the extracted and digested proteins. However, detection limits of gel staining methods have led to a search for complimentary techniques that afford the detection of lower concentrations of biologically relevant proteins. In the present studies, we have evaluated the applicability of on-line capillary electrophoresis - mass spectrometry (CE-MS) for this application. Specifically, we used membrane preconcentration-CE-MS (mPC-CE-MS) to analyze 13 samples of human aqueous humor (AH) from patients with various ocular pathologies (cataract, cataract plus glaucoma, and cataract plus pseudoexfoliation syndrome). This approach enabled rapid analysis of a relatively large volume (1 microL of each specimen, and a protein map for each was created. Measured average molecular weights (Mr) were used to tentatively identify proteins after search of the SWISS-PROT database using TagIdent from ExPaSy. Among those proteins tentatively identified are beta-2 microglobulin (Mr 11731.2), apolipoprotein A1 (Mr 28078.6) and serum albumin (Mr 66400). Proteins with Mr of 4349 (unidentified), 11731.2 (beta-2 microglobulin), 13400-14100 (immunoglobulin fragments), 28078.2 (apolipoprotein A1) and approximately 68000 (serum albumin) were observed in the majority of specimens. Generally no significant differences were noted in the protein composition of aqueous humor samples from different pathologies. However, the absence of an Mr 13345 protein and its oxidized form (Mr 13361) in samples from patients with pseudoexfoliation syndrome was noted. Occasionally the alpha-and beta-chains of hemoglobin, a contaminant in aqueous humor introduced during sampling, were also detected. We conclude from these studies that mPC-CE-MS is an attractive complimentary technique for proteome research, as this approach enables direct mapping and characterization of low concentrations of proteins that are present in complex physiologically derived fluids.
Distinct mechanisms of interferon‐gamma and tumor necrosis factor‐alpha action in oncogene‐transformed mouse fibroblasts (1988)

The potential mechanisms of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha action on tumor cells have been investigated in a model of mouse fibroblasts transformed by distinct retroviral vectors carrying the v-mos, c-myc, and v-Ha-ras oncogene, respectively. Treatment with both cytokines not only caused growth inhibition of v-mos- and c-myc-transformants, but also a reversion of transformation-induced suppression of major histocompatibility complex (MHC) class I antigen expression in all transformed cell lines. The phenotypical reversion of transformants was preceded by a selective modulation of LTR-controlled oncogene expression. TNF-alpha primarily affected stability of oncogene-specific RNAs without influencing the activity of retroviral promoters. In contrast, IFN-gamma was effective at the transcriptional level, apparently due to inhibition of LTR activity as revealed from reduced CAT activity in IFN-gamma-treated LTR-CAT transformants. This IFN-gamma-mediated down-regulation of retroviral promoter activity seemed to be selective for Moloney-virus-derived promoters, since the activity of other viral and cellular promoters was not suppressed by IFN-gamma.
Androgen Receptor Signaling (2004)

Nonsteroidal signaling via the androgen receptor (AR) plays an im-portant role in hormone-refractory prostate cancer. Previously, we have reported that the pleiotropic cytokine, interleukin (IL)-6, inhibited dihydrotestosterone-mediated expression of prostate-specific antigen in LNCaP cells (Jia et al., Mol Can Res 2003;1:385-92). In the present study, we explored the mechanisms involved in this inhibition and considered possible effects on AR nuclear translocation, recruitment of transcription cofactors, and the signaling pathways that may mediate this inhibitory effect. IL-6 neither induced nuclear localization of the AR nor inhibited dihydrotestosterone-induced nuclear translocation of the receptor. IL-6 did not affect AR or p160 coactivator recruitment to the transcription initiation complex on the prostate-specific antigen enhancer and promoter. Moreover, it did not lead to the recruitment of the corepressor silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) or histone deacetylase 1 (HDAC1) at the same sites. IL-6 did, however, prevent the recruitment of the secondary coactivator, p300, to the complex and partially inhibited histone H3 acetylation at the same loci. Furthermore, inhibition by IL-6 was not mediated by the mitogen-activated protein kinase or the Akt pathways and was partially abrogated by signal transducers and activators of transcription-3 knock-down using small interfering RNA. Our results show that IL-6 modulates androgen action through the differential recruitment of cofactors to target genes. These findings may account for the pleiotropic actions of IL-6 in malignant prostate cells.
A Protein Binding Assay for Adenosine 3′:5′-Cyclic Monophosphate (1970)

A simple and sensitive assay for adenosine 3':5'-cyclic monophosphate (cAMP) has been developed that is based on competition for protein binding of the nucleotide, presumably to a cAMP-dependent protein kinase. The nucleotide-protein complex is adsorbed on a cellulose ester filter. Assay conditions are such that a binding constant approaching 10(-9) M is obtained, and the assay is thus sensitive to 0.05-0.10 pmol of cAMP.
Loss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy (1999)

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.
Autologous Primary Muscle-Derived Cells Transfer into the Lower Urinary Tract (2001)

The goal of these experiments was to establish the basic methodology for future clinical applications of muscle-derived cells (MDC) tissue engineering and gene transfer for the treatment of urological dysfunction. Primary MDC isolated via preplating techniques from adult female SD rats were transduced with retrovirus encoding the expression of beta-galactosidase reporter gene. The MDC were injected into the right and left lateral walls of the bladder and proximal urethra of the autologous animals (n = 6) with a 10 microl Hamilton micro syringe. The amount of injected MDC ranged from 1 to 2 x 10(6) cells. The injected tissue was harvested after 7, 14, and 28 days, sectioned and examined histologically for beta-galactosidase and immunohistochemically for fast myosin heavy chain specific to skeletal muscle. The tissues were also stained for anti-CD4 and anti-CD8 antibodies to assess for cellular immune reaction. We have detected a large number of autologous MDC expressing beta-galactosidase and positively stained for fast myosin heavy chain in the bladder and urethral wall. Many injected myoblasts and myotubes were also seen in the bladder and urethral wall at each time point. Staining of lymphocytes with anti-CD4 and anti-CD8 antibodies was negative after MDC injection at each time point. We have demonstrated the long-term survival of autologous MDC and MDC mediated gene transfer into the bladder and urethral wall. Autologous MDC and MDC mediated gene transfer may be a promising treatment to augment bladder and urethral sphincter function.
Bone Metastases in Breast Cancer (2006)

Patients with advanced breast cancer who develop bone metastases suffer from longterm skeletal morbidity. Complications of bone metastases include pain, pathologic fractures, and spinal cord compression, which have a significant impact on the quality of life of patients. Treatment options for patients with bone metastases include surgery, radiation, and analgesics to reduce bone pain and to prevent or repair fractures. Intravenous bisphosphonates can delay the onset of bone metastasis and reduce the percentage of patients who experience skeletal complications of bone metastasis, thus reducing skeletal morbidity. For the past 6 years, pamidronate disodium (90 mg administered by 2-hour intravenous infusion) has been the treatment of choice for the prevention of skeletal complications of bone metastases in patients with breast cancer. However, a more potent bisphosphonate, zoledronic acid (4 mg administered by 15-minute intravenous infusion), was approved for use and has improved efficacy in patients with bone metastases. Because of the increased efficacy and more convenient infusion time, zoledronic acid may become the new standard of care for the treatment and prevention of skeletal complications secondary to bone metastases in patients with breast cancer. Phase III clinical trials have shown that patients with an existing skeletal complication are more likely to develop subsequent complications compared with patients who have not experienced a complication. Therefore, zoledronic acid therapy should be initiated when the patient is diagnosed with bone metastasis.
Organoborane Catalyzed Regioselective 1,4-Hydroboration of Pyridines (2015)

A bulky organoborane Ar(F)2BMe (Ar(F) = 2,4,6-tris(trifluoromethyl)phenyl, 1) has been synthesized. In C6D6 solution this organoborane and pyridine form a frustrated Lewis pair. Under mild conditions, 1 can efficiently catalyze 1,4-hydroboration of a series of pyridines. This reaction is highly chemo- and regioselective. The reaction intermediate, a boronium complex [Py2Bpin][Ar(F)2B(H)Me] (3), was characterized in solution by NMR spectroscopy, which was also confirmed by DFT calculation.
Nucleophilic Substitution Reactions on Sulfur by n-Butyllithium 2 (1987)

The reaction o f some 2-phenylimidaz0[2.1-blbenzothiazoles(1) w i t h organometal reagents in-BuLi, n-Bu2CuLi, i-Pr2NLi and EtMgBr) has been investigated.Two reagents (n-BuLi and n-Bu2CuL1) induced the nucleophilic substitution reaction on s u l f u r o f 1 and t o give the C-S bond cleaved compounds.Previously we reported the reactions o f 2-(p-methoxyphenyl~-6-methylimidazoC2,1-b3benzothfarolew i t h n-butyl l i t h i u m (n-BuLi), followed by quenching w i t h some electrophiles (C02.H20 and p-tolualdehyde) gave the carbon-sulfur bond cleaved compounds (3.3 and s) exclusively. 1'The application o f t h i s reaction t o the derivatives of 9 gave some d i f f e r e n t results.I n t h i s Paper, we describe the reaction o f 2-ip-methylphenyl)-6-methylimidazo~2,1-blbenzothiazole ( E ) 2 3 and 2-Phenyl-6-methylimidazo[2,l-blbenzothiazole w i t h n-BuLi and the reaction of 5 w i t h other organometal reagents.Compound was allowed t o react w i t h 1 equiv of n-BuLi i n tetrahydrofuran (THF) f o r 30 min a t -70-C under argon.The reaction mixture was quenched w i t h carbon dioxide (Cop) a t -60.C t o give three products differed from the r e s u l t o f the reaction o f 5 and n-BuLi, which gave only C-S bond cleaved product I n addition to the major product (E, 32%).the C-S bond cleaved
Comparison of biotinylated DNA and RNA probes for rapid detection of varicella-zoster virus genome by in situ hybridization (1991)

We describe a general method for the production of nonisotopic DNA and RNA probes for the detection of the varicella-zoster virus (VZV) genome by in situ hybridization. VZV DNA was extracted from purified viral nucleocapsids, cleaved with restriction enzyme (RE) BamHI, and cloned into plasmid pBR322 by the standard vector insert procedure. We cloned over 85% of the VZV genome and obtained 18 recombinants. Plasmids containing the B, F, G, H, and J fragments of VZV DNA were labeled by the nick translation method with biotin-11-dUTP as the dTTP analog. Additionally, the B fragment was cleaved with RE AvaI, subcloned into the plasmid pGEM-4 transcription vector, and subsequently linearized with REs PstI and EcoRI. RNA was transcribed with T7 or SP6 polymerase, with a substitution of allylamine-UTP as the UTP analog, and labeled with epsilon-caproylamidobiotin-N-hydroxysuccinimide ester. The DNA and RNA probes were used under full-stringency conditions for in situ hybridization with alkaline phosphatase as the detector and 5-bromo-4-chloro-3-indolyl phosphate-Nitro Blue Tetrazolium as the substrate. When tested under comparable conditions, the RNA probe was slightly more sensitive than was the DNA probe: both probes showed homology only with VZV-infected cells and clinical tissues and not with the other herpesviruses. Probes prepared from variable regions of the genome (fragments F and J) performed as well as did those from conserved regions (fragments B. G. and H). Biotinylated probes have distinct advantages over isotopic probes and retain their full potency for more than 2 years when stored properly.
Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME‐esterase activity (1991)

The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10‐fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME‐esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME‐esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME‐esterase levels and the tryptase levels (r = 0.71; P &lt; 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non‐allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
A simple, reliable waveguide dye laser for ophthalmological applications (1975)

The principle of operation, construction, and performance of a compact waveguide dye laser, especially designed as a source of retinal photocoagulators, are described, The guiding effects produced by the thermal gradients induced by the pumping pulse and the use of closed resonator make the laser very reliable, simple, and with good pulse repeatibility. The construction is very simple and inexpensive. Except for flashlamps, which are commercial, no part of the laser requires sophisticated technology to be built or assembled; neither optical components have critical flatness and need careful alignment. The system does not need cooling, and slow recirculation of the solution, necessary to replace the degraded dye in the waveguide, is provided by a magnetically coupled 0.1 W electric motor. The dye cell, pump, and dye reservoir form a single component of the laser which can be easily extracted for inspection and replacement of the dye solution. The single, regular pulse emitted by the laser, its time duration (a few microseconds), the possibility to operate the laser at the absorption peaks of the ocular tissues make the laser better than the random spiking ’’passive’’ ruby laser or than the ’’explosive’’ Q−switched ruby laser for ophthalmological applications. If connected with a slit lamp, the laser should compete with the much more expensive ion gas lasers. Good retinal photocoagulations have been made in rabbits using a solution of Rhodamine 6G in ethanol. Retinal spots of rectangular shape of variable dimension but of constant energy density have veen produced by simply masking the exit window of the laser.