gebhart/patrepeval huggingface dataset:
Rational Design of Potentiometric Trace Level Ion Sensors. A Ag+-Selective Electrode with a 100 ppt Detection Limit (2002)

Submicromolar to picomolar lower detection limits have recently been obtained with various polymer membrane ion-selective electrodes by minimizing biases due to ion fluxes through the membrane. For the best performance, the compositions of the membrane and inner solution should be optimized for each application. Given the number of parameters to be adjusted, it has been difficult to find the best parameters for a target sample. In this paper, a much simplified and more practical steady-state model of zero-current ion fluxes is derived, which is based on measurable parameters. The model allows one to predict achievable lower detection limits for a membrane with given selectivities. It can also be used to predict the optimal composition of the inner filling solution for the measurement of samples with a known, typical ionic background. Selectivity coefficients of monovalent and divalent analyte ions required for desired detection limits in drinking water are calculated. As an application of the proposed general recipe, a silver-selective electrode is developed on the basis of the ionophore O,O''-bis[2-(methylthio)ethyl]-tert-butylcalix[4]arene. With the predicted optimal composition of the inner electrolyte, its lower detection limit is found to be 10(-9) M or 100 ppt Ag+ with an ionic background of 10(-5) M LiNO3, which is very close to the expected value.
Safety and efficacy of intravenous iron polymaltose, iron sucrose and ferric carboxymaltose in pregnancy: A systematic review (2017)

While IV iron in pregnancy improves haematological parameters, there is an absence of evidence for improvements in important maternal or perinatal outcomes. No single preparation of IV iron appeared to be superior, with the current IV iron preparation of choice largely determined by cost and convenience around administration.
Multiple Non-LTR Retrotransposons in the Genome of Arabidopsis thaliana (1996)

DNA sequence analysis near the Arabidopsis thaliana ABI3 gene revealed the presence of a non-LTR retrotransposon insertion that we have designated Ta11-1. This insertion is 6.2 kb in length and encodes two overlapping reading frames with similarity to non-LTR retrotransposon proteins, including reverse transcriptase. A polymerase chain reaction assay was developed based on conserved amino acid sequences shared between the Ta11-1 reverse transcriptase and those of non-LTR retrotransposons from other species. Seventeen additional A. thaliana reverse transcriptases were identified that range in nucleotide similarity from 48-88% (Ta12-Ta28). Phylogenetic analyses indicated that the A. thaliana sequences are more closely related to each other than to elements from other organisms, consistent with the vertical evolution of these sequences over most of their evolutionary history. One sequence, Ta17, is located in the mitochondrial genome. The remaining are nuclear and of low copy number among 17 diverse A. thaliana ecotypes tested, suggesting that they are not highly active in transposition. The paucity of retrotransposons and the small genome size of A. thaliana support the hypothesis that most repetitive sequences have been lost from the genome and that mechanisms may exist to prevent amplification of extant element families.
Effect of Saturating Cation, pH, and Aluminum and Iron Oxide on the Flocculation of Kaolinite and Montmorillonite (1987)

Abstract The effect of pH on the flocculation-dispersion behavior of noncrystalline aluminum and iron oxides, kaolinite, montmorillonite, and various mixtures of these materials was investigated. The clays were Na- or Ca-saturated and freeze-dried before use. Critical coagulation concentrations (CCC) of all materials and mixtures were found to be pH dependent. The Al oxide was flocculated at pH &gt;9.5 and the iron oxide was flocculated between pH 6.0 and 8.2; i.e., flocculation occurred at pHs near the point of zero charge (PZC). The CCC of both the Na- and Ca-clay systems increased with increasing pH. The effect of pH was greater for the Na-kaolinite (flocculated at pH 5.8 and having a CCC of 55 meq/liter at pH 9.1) than the Na-montmorillonite system (having a CCC of 14 meq/liter at pH 6.4 and a CCC of 28 meq/liter at pH 9.4). A 50/50 mixture of Na-kaolinite and Na-montmorillonite behaved more like montmorillonite (having CCCs of 13 and 33 meq/liter at pH 6.2 and pH 9.0, respectively). The presence of either noncrystalline oxide decreased the CCC over that of the clay(s) alone; the decrease occurred at pHs &gt;7 for Al oxide and at pHs &gt;6.5 for Fe oxide. Aluminum oxide produced a greater decrease in CCC than Fe oxide, especially at pHs &gt;8. The effect of each oxide on CCC was greatest near the PZC, 9.5 and 7.2 for Al and Fe oxide, respectively.
Binding of Hoechst 33258 to the TAR RNA of HIV-1. Recognition of a pyrimidine bulge-dependent structure (1997)

The transactivation response region (TAR) RNA is an essential component in transcriptional regulation of the human immunodeficiency virus type-1 (HIV-1) genome. We have examined the interaction between TAR RNA and the bisbenzimidazole derivative Hoechst 33258. Previous studies have shown that this drug, which is well known as an AT-selective DNA minor groove binder, can also interact with GC-rich sequences in DNA as well as with RNA, possibly by intercalation. Absorption spectroscopy, circular dichroism and electric linear dichroism, as well as RNase A footprinting, were employed to compare binding of Hoechst 33258 to wild-type RNA and its analogue lacking the pyrimidine bulge. The uridine bulge, which is an important contributor to the structural stability of TAR, plays an essential role in drug binding. Deletion of the bulge destabilizes both free and drug-bound forms of TAR and markedly affects the orientation of the drug chromophore complexed with the RNA. According to the linear dichroism data, the bisbenzimidazole is oriented more or less perpendicular to the RNA helix axis. The data are compatible with a model in which the bisbenzimidazole chromophore is inserted into the existing cavity created by the pyrimidine bulge. The footprinting experiments, showing that the drug binds to a unique site opposite the unpaired uridine residues, also support this model. The binding of Hoechst 33258 to the sequence 5'-GCUCU, which delimits the cavity, reflects the greater accessibility of that region compared with other sites in the RNA molecule. The identification of a binding site for small molecules in TAR offers promising perspectives for developing drugs that would block the access of TAR RNA to proteins and therefore for the design of anti-HIV agents.
Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. (1988)

Studies were designed to explore the possibility that human polymorphonuclear leukocyte granule constituents in addition to elastase (HLE) had the potential to cause emphysema. A two-step purification of three serine proteinases was developed. Granule extract proteins were initially separated by dye-ligand affinity chromatography. Fractions eluted were divided into four pools. Hamsters were given a single intratracheal instillation of saline +/- 0.1 mg protein of each pool. While pool 2 contained HLE and cathepsin G, the most dramatic bullous emphysema developed in animals treated with pool 4. The esterase from pool 4, designated proteinase 3 (PR-3) was purified, characterized in vitro, and tested for its ability to cause emphysema. PR-3 is a neutral serine proteinase with isoenzyme forms. Its ability to degrade elastin at pH 6.5 is slightly greater than that of HLE, but it is less active than HLE at pH 7.4 or 8.9. PR-3 has weak activity against azocasein. Its ability to degrade hemoglobin is intermediate to that of HLE and cathepsin G at pH 7.4. PR-3 has no activity against chromogenic substrates specific for HLE or cathepsin G. Its pI is substantially less than HLE or cathepsin G. It is also immunologically distinct from HLE. It induces emphysema in hamsters commensurate with that of HLE. We conclude that PR-3 may be important in the pathogenesis of human emphysema.
The Future of DNA Sequencing (1993)

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Lipid-Conjugated 27-Nucleotide Double-Stranded RNAs with Dicer-Substrate Potency Enhance RNAi-Mediated Gene Silencing (2012)

Short interfering RNAs (siRNAs), used in RNA interference (RNAi) technology, are powerful tools for target-gene silencing in a sequence-specific manner. In this study, Dicer-substrate 27-nucleotide (nt) double-stranded RNAs (dsRNAs), which are known to have a highly potent RNAi effect, were conjugated with palmitic acid at the 5'-end of the sense strand to enhance intracellular delivery and RNAi efficacy. The palmitic acid-conjugated 27-nt dsRNAs (C16-ds27RNAs) were prepared by our simple synthesis strategy in good yield. The C16-ds27RNAs were cleaved by a Dicer enzyme, leading to the release of 21-nt siRNAs. The high level of stability in serum using C16-ds27RNAs was also confirmed. The C16-ds27RNAs showed enhanced RNAi potency targeted to both an exogenous luciferase and an endogenous vascular endothelial growth factor (VEGF) gene in the presence or absence of a transfection reagent, such as Lipofectamine 2000. In addition, the C16-ds27RNAs had a more potent gene-silencing activity than the other lipid-conjugated 21-nt siRNAs and 27-nt dsRNAs. The C16-ds27RNAs also exhibited significant membrane permeability. These results suggested that the C16-ds27RNAs will be useful for next-generation RNAi molecules that can address the problems of RNAi technology.
Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. (2000)

Photodynamic therapy (PDT) is a promising cancer treatment that induces localized tumor destruction via the photochemical generation of cytotoxic singlet oxygen. PDT-mediated oxidative stress elicits direct tumor cell damage as well as microvascular injury within exposed tumors. Reduction in vascular perfusion associated with PDT-mediated microvascular injury produces tumor tissue hypoxia. Using a transplantable BA mouse mammary carcinoma, we show that Photofrin-mediated PDT induced expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) subunit of the heterodimeric HIF-1 transcription factor and also increased protein levels of the HIF-1 target gene, vascular endothelial growth factor (VEGF), within treated tumors. HIF-1alpha and VEGF expression were also observed following tumor clamping, which was used as a positive control for inducing tissue hypoxia. PDT treatment of BA tumor cells grown in culture resulted in a small increase in VEGF expression above basal levels, indicating that PDT-mediated hypoxia and oxidative stress could both be involved in the overexpression of VEGF. Tumor-bearing mice treated with combined antiangiogenic therapy (IM862 or EMAP-II) and PDT had improved tumoricidal responses compared with individual treatments. We also demonstrated that PDT-induced VEGF expression in tumors decreased when either IM862 or EMAP-II was included in the PDT treatment protocol. Our results indicate that combination procedures using antiangiogenic treatments can improve the therapeutic effectiveness of PDT.
Expression and transcriptional activity of Ap‐1, CRE, and URE binding proteins in B16 mouse melanoma subclones (1994)

The expression and DNA binding activity of members of the activating protein-1 (AP-1) and activating transcription factor (ATF) families of transcription factors were analyzed in sham and ultraviolet (UV)-irradiated subclones of the B16 mouse melanoma cell system. The four subclones we used represent sequential stages in the development and progression of malignant melanoma and exhibit differences in growth and metastatic potential. Western blot analysis revealed differential expression of some AP-1 (c-jun, jun-B, and jun-D) and ATF (43- and 47-kDa cyclic AMP-responsive element binding protein (CREB) family members) in the different subclones; while c-jun expression was noted in the subclones with the greater malignant potential, jun-D was expressed in those with the lesser malignant potential. Furthermore, a delicate balance between the two forms of CREB was noted; the 47-kDa CREB appeared, when expressed exclusively, in subclones that exhibit a greater malignant potential. Electrophoretic mobility shift assays using AP-1, CRE, and UV-responsive element (URE) consensus sequences indicated that distinct complexes were formed with extracts from each of the four subclones. The complexes were competitively inhibited by each of the target sequences used, suggesting that "cross-talk" occurs between some AP-1 and ATF family members in this cell system. Moreover, a multimer of the URE sequence, cloned upstream of a chloramphenicol acetyltransferase reporter gene, was transcriptionally active and responsive to UV irradiation in two of the four subclones. UV-related transcriptional activation was directly correlated with the expression of a 43-kDa CREB. Together, these observations identify members of AP-1 and CREB families whose expression and activities correlate with the malignant potential of subclones that represent different stages in melanoma development and progression.
Broadband on-chip near-infrared spectroscopy based on a plasmonic grating filter array (2016)

We demonstrate an ultra-compact, broadband on-chip near-infrared (NIR) spectroscopy system based on a narrow-band plasmonic filter array. The entire filter array, consisting of 28 individual subwavelength metallic gratings, was monolithically integrated in a thin gold film on a quartz substrate, covering a 270 nm spectra from 1510 nm to 1780 nm. In order to achieve a high spectral resolution, extremely narrow slits are created for the gratings with a polymer waveguide layer on top, generating narrow-band guided-mode resonances through coupling with the surface-plasmon resonances of the metallic gratings. Experimental results show that the transmission bands of the filter array have full width at half-maximum of only 7 nm-13 nm, which is sufficient for NIR spectroscopy. The NIR absorption spectroscopy of xylene using the on-chip plasmonic filter array matches very well with the results from conventional Fourier transform infrared spectroscopy, which proves the great potential for NIR sensing applications.
Nuclear magnetic resonance – from molecules to man (1987)

Initial observations of the physical phenomenon of nuclear magnetic resonance (NMR) date back to the late 1940s. In the following two decades high-resolution NMR in solution became an indispensible analytical tool in chemistry, and solid state NMR had an increasingly important role in physics. Some of the potentialities of the method for investigations of complex biological systems had also long been anticipated, and initial experiments with biological specimens were described already 30 years ago. In practice, however, biological applications of NMR have become really attractive only during the last decade, following revolutionary advances in NMR instrumentation and the methodology for their use. NMR projects in biology and medicine now include studies of biomacromolecular structure and function, work on biological membranes, in vivo studies of biochemical processes, and imaging of macroscopic objects. Because of imminent practical applications in medical diagnosis and thanks to extensive coverage by the popular news media, interest in some of the recent developments spreads far beyond the scientific community, making NMR a widely popular field.
A common translational control mechanism functions in axial patterning and neuroendocrine signaling inDrosophila (2002)

Translational repression of maternal nanos (nos) mRNA by a cis-acting Translational Control Element (TCE) in the nos 3'UTR is critical for anterior-posterior patterning of the Drosophila embryo. We show, through ectopic expression experiments, that the nos TCE is capable of repressing gene expression at later stages of development in neuronal cells that regulate the molting cycle. Our results predict additional targets of TCE-mediated repression within the nervous system. They also suggest that mechanisms that regulate maternal mRNAs, like TCE-mediated repression, may function more widely during development to spatially or temporally control gene expression.
Dimeric Amyloid β Protein Rapidly Accumulates in Lipid Rafts followed by Apolipoprotein E and Phosphorylated Tau Accumulation in the Tg2576 Mouse Model of Alzheimer's Disease (2004)

To investigate lipid rafts as a site where amyloid beta protein (Abeta) oligomers might accumulate and cause toxicity in Alzheimer's disease (AD), we analyzed Abeta in the Tg2576 transgenic mouse model of AD. Abeta was highly concentrated in lipid rafts, which comprise a small fraction of brain volume but contain 27% of brain Abeta42 and 24% of Abeta40 in young mice. In the Tg2576 model, memory impairment begins at 6 months before amyloid plaques are visible. Here we show that Abeta dimers appear in lipid rafts at 6 months and that raft Abeta, which is primarily dimeric, rapidly accumulates reaching levels >500x those in young mice by 24-28 months. A similar large accumulation of dimeric Abeta was observed in lipid rafts from AD brain. In contrast to extracellular amyloid fibrils, which are SDS-insoluble, virtually all Abeta in lipid rafts is SDS soluble. Coupled with recent studies showing that synthetic and naturally occurring Abeta oligomers can inhibit hippocampal long-term potentiation, the in vivo age-dependent accumulation of SDS-soluble Abeta dimers in lipid rafts at the time when memory impairment begins in Tg2576 mice provides strong evidence linking Abeta oligomers to memory impairment. After dimeric Abeta began to accumulate in lipid rafts of the Tg2576 brain, apolipoprotein E (ApoE) and then phosphorylated tau accumulated. A similar increase in ApoE and a large increase in phosphorylated tau was observed in lipid rafts from AD brain. These findings suggest that lipid rafts may be an important site for interaction between dimeric Abeta, ApoE, and tau.
Anaphylaxis: can we tell who is at risk of a fatal reaction? (2004)

Most fatal anaphylactic reactions are unpredictable. The appropriate management after recovery from a severe reaction may be protective against a fatal recurrence. An accurate identification of the cause and effective avoidance is a crucial part of this management, together with effective treatment of asthma for those with food allergy, immunotherapy for sting allergy, the avoidance of drugs that potentiate anaphylaxis, and effective training in self-treatment.
Update on PML and PML-IRIS Occurring in Multiple Sclerosis Patients Treated With Natalizumab (2012)

The use of natalizumab to treat multiple sclerosis (MS) has been associated with the development of progressive multifocal leukoencephalopathy (PML), with 242 PML cases reported as of May 3, 2012. Fortunately, rapid withdrawal of the drug and administration of plasma exchange has allowed survival in many of these patients, but a new problem, immune reconstitution inflammatory syndrome (IRIS), has emerged after drug withdrawal. This report provides an update on PML in natalizumab-treated patients and reviews what is currently known about PML-IRIS in this setting; autopsy findings from a well-studied patient are illustrated. This patient with relapsing-remitting MS had been treated for 4 years with natalizumab, with discontinuation of drug after diagnosis of PML by cerebrospinal fluid polymerase chain reaction testing. Disease was manifested by severe paraparesis and expressive aphasia, which progressed before and after the diagnosis of PML. Immune reconstitution inflammatory syndrome was diagnosed, comfort care was instituted, but demise did not occur until 9 months later. Autopsy showed ongoing severe PML-IRIS, with massive cavitary brain lesions containing abundant perivascular and parenchymal CD8-positive T-cell infiltrates. Bone marrow and spleen, but not brain, contained monoclonal T-cell populations by polymerase chain reaction-based gene rearrangement studies, indicating overstimulation of peripheral T cells; T-cell lymphoma was not identified by morphological or immunohistochemical criteria.
Characterization and mapping of monoclonal antibodies against the Sleeping disease virus, an aquatic alphavirus (2005)

Sleeping disease virus (SDV) is an emerging pathogen in salmonid aquacultures, the impact of which is underestimated to date due to the lack of efficient diagnostic tools. To better characterize this new aquatic alphavirus and to make molecular tools available, a panel of monoclonal antibodies (mAbs) directed against SDV non-structural and structural proteins has been generated by immunizing mice with SDV-specific recombinant proteins overexpressed in Escherichia coli as antigens. So far, mAbs against nsP1, nsP3, E2 and E1 SDV proteins have been produced and their reactivity has been characterized by Western blot, radioimmunoprecipitation and indirect immunofluorescence assays. In addition, protein domains recognized by each mAb have been determined by immunofluorescence assay on truncated expressed SDV-derived proteins. Finally, one mAb directed against the E1 glycoprotein has been evaluated as a potential tool to be used in immunohistochemistry assay on experimentally infected trout.
Chicken and Xenopus Mannose 6-Phosphate Receptors Fail to Bind Insulin-like Growth Factor II (1989)

The recent demonstration that a single mammalian receptor protein binds both mannose 6-phosphate (Man-6-P) and insulin-like growth factor II (IGF-II) with high affinity has suggested a multifunctional physiological role for this receptor, possibly including signal transduction. In order to better understand the functions of this receptor, we have investigated the properties of Man-6-P receptors from non-mammalian species. Receptors were affinity-purified from Triton X-100 extracts of total membranes from Xenopus and chicken liver as well as rat placenta using pentamannosyl 6-phosphate-Sepharose. The Man-6-P receptor was adsorbed to the pentamannosyl 6-phosphate-Sepharose and specifically eluted by Man-6-P in all three species, as evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining. When the purified receptors from these three species were cross-linked to 125I-IGF-II with disuccinimidyl suberate, only receptors isolated from rat membranes were affinity-labeled. To further evaluate the properties of these Man-6-P receptors, binding of 125I-rat-IGF-II and 125I-chicken Tyr-Gly-Thr-Ala-IGF-II to purified receptors from Xenopus, chicken, and rat was evaluated by polyethylene glycol precipitation. Only the rat Man-6-P receptor exhibited detectable binding of 125I-IGF-II. These data suggest that the emergence of a high affinity IGF-II binding site on the Man-6-P receptor occurred in evolution after the divergence of mammals from other vertebrates. Thus, the biological actions of IGF-II in chickens and frogs appear to be initiated by the type I IGF receptor.