gebhart/patrepeval huggingface dataset:
Synthesis and Evaluation of 11C-Labeled 6-Substituted 2-Arylbenzothiazoles as Amyloid Imaging Agents (2003)

The synthesis and evaluation of a series of neutral analogues of thioflavin-T (termed BTA's) with high affinities for aggregated amyloid and a wide range of lipophilicities are reported. Radiolabeling with high specific activity [(11)C]methyl iodide provided derivatives for in vivo evaluation. Brain entry in control mice and baboons was high for nearly all of the analogues at early times after injection, but the clearance rate of radioactivity from brain tissue varied by more than 1 order of magnitude. Upon the basis of its rapid clearance from normal mouse and baboon brain tissues, [N-methyl-(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]6-OH-BTA-1) was selected as the lead compound for further evaluation. The radiolabeled metabolites of [(11)C]6-OH-BTA-1 were polar and did not enter brain. The binding affinities of [N-methyl-(3)H]6-OH-BTA-1 for homogenates of postmortem AD frontal cortex and synthetic Abeta(1-40) fibrils were similar (K(d) = 1.4 nM and 4.7 nM, respectively), but the ligand-to-Abeta peptide binding stoichiometry was approximately 400-fold higher for AD brain than Abeta(1-40) fibrils. Staining of AD frontal cortex tissue sections with 6-OH-BTA-1 indicated the selective binding of the compound to amyloid plaques and cerebrovascular amyloid. The encouraging in vitro and in vivo properties of [(11)C]6-OH-BTA-1 support the choice of this derivative for further evaluation in human subject studies of brain Abeta deposition.
Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models (2013)

RET gene fusions are recurrent oncogenes identified in thyroid and lung carcinomas. Lenvatinib is a multi-tyrosine kinase inhibitor currently under evaluation in several clinical trials. Here we evaluated lenvatinib in RET gene fusion-driven preclinical models. In cellular assays, lenvatinib inhibited auto-phosphorylation of KIF5B-RET, CCDC6-RET, and NcoA4-RET. Lenvatinib suppressed the growth of CCDC6-RET human thyroid and lung cancer cell lines, and as well, suppressed anchorage-independent growth and tumorigenicity of RET gene fusion-transformed NIH3T3 cells. These results demonstrate that lenvatinib can exert antitumor activity against RET gene fusion-driven tumor models by inhibiting oncogenic RET gene fusion signaling.
Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins. (1990)

The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen preparations could protect susceptible monkeys from an otherwise lethal malaria infection. In contrast to the natural antigen, recombinant p41 protein (P. falciparum aldolase) could not protect monkeys, although all animals seroconverted. 190N antigen, a recombinant protein containing conserved sequences of the major merozoite surface antigen p190, protected two of five monkeys from critical levels of infection with the highly virulent FVO isolate of P. falciparum. However, the B- and T-cell responses to 190N antigen were similar in protected and unprotected animals so that other unknown factors may contribute to protection. Higher purity or lack of protective epitopes or different structure of protective epitopes in the recombinant proteins might explain the better performance of parasite-derived antigens in vaccination trials. The partial protection obtained with 190N antigen suggests that this molecule could contribute to a vaccine mixture against P. falciparum.
Blockade of Long-Term Potentiation by β-Amyloid Peptides in the CA1 Region of the Rat Hippocampus In Vivo (2001)

The effect of intracerebroventricular (icv) injections of β-amyloid peptide fragments Aβ[15–25], Aβ[25–35], and Aβ[35–25] were examined on synaptic transmission and long-term potentiation (LTP) in the hippocampal CA1 region in vivo. Rats were anesthetized using urethan, and changes in synaptic efficacy were determined from the slope of the excitatory postsynaptic potential (EPSP). Baseline synaptic responses were monitored for 30 min prior to icv injection of Aβ peptides or vehicle. High-frequency stimulation (HFS) to induce LTP was applied to the Schaffer-collateral pathway 5 min or 1 h following the icv injection. HFS comprised 3 episodes of 10 stimuli at 200 Hz, 10 times, applied at 30-s intervals. Normal LTP measured 30 min following HFS, was produced following icv injection of vehicle (191 ± 17%, mean ± SE, n = 6) or Aβ[15–25; 100 nmol] (177 ± 6%, n = 6) 1 h prior to HFS. LTP was, however, markedly reduced by Aβ[25–35; 10 nmol] (129 ± 9%, n = 6, P &lt; 0.001) and blocked by Aβ[25–35; 100 nmol] (99 ± 6%, n = 6, P &lt; 0.001). Injection of the reverse peptide, Aβ[35–25], also impaired LTP at concentrations of 10 nmol (136 ± 3%, n = 6, P &lt; 0.01) and 100 nmol (144 ± 7, n = 8, P &lt; 0.05). Using a different protocol, HFS was delivered 5 min following Aβ injections, and LTP was measured 1 h post HFS. Stable LTP was produced in the control group (188 ± 15%, n = 7) and blocked by Aβ[25–35, 100 nmol] (108 ± 15%, n = 6, P &lt; 0.001). A lower dose of Aβ[25–35; 10 nmol] did not significantly impair LTP (176 ± 30%, n = 4). The Aβ-peptides tested were also shown to have no significant effect on paired pulse facilitation (interstimulus interval of 50 ms), suggesting that neither presynaptic transmitter release or activity of interneurons in vivo are affected. The effects of Aβ on LTP are therefore likely to be mediated via a postsynaptic mechanism. This in vivo model of LTP is extremely sensitive to Aβ-peptides that can impair LTP in a time- ([25–35]) and concentration-dependent manner ([25–35] and [35–25]). These effects of Aβ-peptides may then contribute to the cognitive deficits associated with Alzheimer's disease.
A novel method for determining the anchoring energy function at a nematic liquid crystal-wall interface from director distortions at high fields (1985)

We show that the anchoring energy function, i.e., the anisotropic part of the interfacial free energy, at a nematic liquid crystal-wall interface can be determined uniquely without a numerical fitting procedure, when the integrated birefringence of a liquid crystal cell with a thickness much larger than the extrapolation length is measured as a function of an electric or magnetic field well above the Freedericksz threshold. The precision of the present method is closely argued, showing that the resulting anchoring energy function is reasonably insensitive to the uncertainties in the material parameters and in the cell thickness. As an example, the anchoring energy function at the interface between 5CB(pentylcyanobiphenyl) and an obliquely evaporated SiO was determined for the first time, by measuring the birefringence and the capacitance of a 56-μm-thick cell up to 150 V rms at 0.23 °C below the clearing temperature. A saturation of the field-induced distortion was clearly observed at about 100 V rms. The anchoring energy function was found to be well fitted by a function of the form (1)/(2) Ea sin2 θ+ (1)/(4) E1 sin4 θ, where θ is the angle between the boundary director and the substrate, with Ea ∼4.0×10−5 J/m2 and E1∼−1.8×10−5 J/m2.
Cleavable Hydrophilic Linker for One-Bead-One-Compound Sequencing of Oligomer Libraries by Tandem Mass Spectrometry (2006)

We have developed a method for the rapid and unambiguous identification of sequences of hit compounds from one-bead-one-compound combinatorial libraries of peptide and peptoid ligands. The approach uses a cleavable linker that is hydrophilic to help reduce nonspecific binding to biological samples and allows for the attachment of a halogen tag, which greatly facilitates post-screening sequencing by tandem mass spectrometry (MS/MS). The linker is based on a tartaric acid unit, which, upon cleavage from resin, generates a C-terminal aldehyde. This aldehyde can then be derivatized with a bromine-containing amino-oxy compound that serves as an isotope tag for subsequent MS/MS analysis of y-ion fragments. We have applied this linker and method to the syntheses of a number of peptoids that vary in sequence and length and have also demonstrated single-bead sequencing of a peptoid pentamer. The linker is also shown to have very low levels of nonspecific binding to proteins.
Preparative Soft and Reactive Landing of Multiply Charged Protein Ions on a Plasma-Treated Metal Surface (2005)

Soft landing on a plasma-treated metal surface of multiply protonated protein ions from the gas phase results in a substantial retention of protein function, as demonstrated for trypsin and streptavidin. The majority of trypsin ions soft-landed at hyperthermal kinetic energies are undamaged and retain 72-98% of enzymatic activity after being washed into solution. A small fraction of trypsin ions that were landed at nominal kinetic energies of 130-200 eV remain tethered to the surface and show approximately 50% enzymatic activity. The streptavidin tetramer is found to dissociate to monomer units upon multiple charging in electrospray. The majority of soft-landed monomers can be washed into solution where they show affinity to biotin. The layer of streptavidin monomer that is immobilized on the surface can be detected if fluorescence-tagged and retains the ability to reversibly bind biotin. A mechanism is proposed to explain nondestructive protein ion discharge on the surface that considers proton migration from the soft-landed cations to the metal oxide layer and metal ion reduction by electron transfer from the bulk metal.
Linear Optical Quantum Computing in a Single Spatial Mode (2013)

We present a scheme for linear optical quantum computing using time-bin-encoded qubits in a single spatial mode. We show methods for single-qubit operations and heralded controlled-phase (cphase) gates, providing a sufficient set of operations for universal quantum computing with the Knill-Laflamme-Milburn [Nature (London) 409, 46 (2001)] scheme. Our protocol is suited to currently available photonic devices and ideally allows arbitrary numbers of qubits to be encoded in the same spatial mode, demonstrating the potential for time-frequency modes to dramatically increase the quantum information capacity of fixed spatial resources. As a test of our scheme, we demonstrate the first entirely single spatial mode implementation of a two-qubit quantum gate and show its operation with an average fidelity of 0.84±0.07.
Factors governing helical preference of peptides containing multiple alpha,alpha-dialkyl amino acids. (1990)

The presence of multiple alpha,alpha-dialkyl amino acids such as alpha-methylalanine (alpha-aminoisobutyric acid, Aib) leads to predominantly helical structures, either with alpha-helical or 3(10)-helical hydrogen bonding patterns. The crystal structure of emerimicin-(1-9) benzyl ester (Ac-Phe-Aib-Aib-Aib-Val-Gly-Leu-Aib-Aib-OBzl) reported here shows essentially pure alpha-helical character, whereas other similar compounds show predominantly 3(10)-helical structures. The factors that govern helical preference include the inherent relative stability of the alpha-helix compared with the 3(10)-helix, the extra hydrogen bond seen with 3(10)-helices, and the enhanced electrostatic dipolar interaction of the 3(10)-helix when packed in a crystalline lattice. The balance of these forces, when combined with the steric requirements of the amino acid side chains, determines the relative stability of the two helical conformations under a given set of experimental conditions.
Effect of FUT-175, a new synthetic protease inhibitor, on the development of lupus nephritis in (NZB x NZW) F1 mice. (1985)

FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulphonate), a new synthetic protease inhibitor, was administrated to (NZB x NZB) F1 mice in order to examine its influence on the development of autoimmune diseases. A dose (400 mg/kg of body weight) of FUT-175 has both prophylactic and curative effects on the development of lupus nephritis: mice showed a significantly low percentage of proteinuria, a marked decrease in BUN levels, and the lowest degree of glomerular damages. Dexamethasone had almost the same effect as FUT-175 (400 mg/kg), but it was slightly less effective than FUT-175. These results suggest that the administration of FUT-175 may become a viable strategy for the treatment of human autoimmune diseases.
RNA secondary structure prediction by centroids in a Boltzmann weighted ensemble (2005)

Prediction of RNA secondary structure by free energy minimization has been the standard for over two decades. Here we describe a novel method that forsakes this paradigm for predictions based on Boltzmann-weighted structure ensemble. We introduce the notion of a centroid structure as a representative for a set of structures and describe a procedure for its identification. In comparison with the minimum free energy (MFE) structure using diverse types of structural RNAs, the centroid of the ensemble makes 30.0% fewer prediction errors as measured by the positive predictive value (PPV) with marginally improved sensitivity. The Boltzmann ensemble can be separated into a small number (3.2 on average) of clusters. Among the centroids of these clusters, the "best cluster centroid" as determined by comparison to the known structure simultaneously improves PPV by 46.5% and sensitivity by 21.7%. For 58% of the studied sequences for which the MFE structure is outside the cluster containing the best centroid, the improvements by the best centroid are 62.5% for PPV and 31.4% for sensitivity. These results suggest that the energy well containing the MFE structure under the current incomplete energy model is often different from the one for the unavailable complete model that presumably contains the unique native structure. Centroids are available on the Sfold server at http://sfold.wadsworth.org.
ON THE FAST TRACK TO SUCCESS IN ECUADOR (2005)

This article describes the San Francisco Hydroelectric Power Project under construction in Ecuador. Designed to bring relief to Ecuador’s current power deficit, the project is located completely underground and involves the construction of a 9km long hard rock tunnel boring machine (TBM) drive. The article gives an overview of the geology of the region and the various excavation procedures that have been used. The project is expected to increase the power capacity in Ecuador by close to 12 percent.
PCR cloning protocols : from molecular cloning to genetic engineering (1997)

The advent of PCR, with its power to amplify tiny amounts of DNA, quickly spawned the development of many analytical procedures that are widely used for detection, measurement, and characterization. However, creative investigators soon discovered the power of PCR for synthetic or preparative uses. This volume focuses on such preparative PCR protocols, which can be used in the cloning and modification of DNA. PCR Cloning Protocols: From Molecular Cloning to Genetic Engineer­ ing is divided into seven parts, each containing a collection of chapters address­ ing a general approach or goal. Part I presents basic PCR protocols, emphasizing optimizing conditions for (he amplification of DNA fragments of several kilobases in length. Part 11 offers several procedures for cloning PCR prod­ ucts, depending on whether a specific restriction site can be used in the clon­ ing vector, the PCR product is to be gel purified before cloning, or the fragmeni needs to be inserted in one or both orientations. Part III includes several pro­ tocols involved in the mutagenesis of DNA, either site-directed or not, as well as several approaches to recombinant PCR, either for mutagenesis or building a custom gene, as well as one chapter describing a specific use of in vitro selection. Part IV addresses the frequent need to amplify and clone segments of DNA that are to the right, left, or scattered within a stretch of DNA (either vector, chromosomal, or cDNA) of known sequence
AN EHF backplate design for airborne active phased array antennas (2002)

An EHF array backplate design for use in airborne active phase array antennas is described. The backplate utilizes a multilayer substrate and reduced waveguide for signal routing, while a counterflow air cooling technique is used to cool the GaAs monolithic microwave integrated circuit (MMIC) active devices. The integrated design is characterized by temperature-coefficient-matched materials to insure a rigid, thermally stable structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
PP.11.21 (2015)

Objective: UUO model not only induces renal interstitial fibrosis(RIF) in obstructed kidney, but also induces injury in contralateral kidney. The precise mechanisms to induce RIF in the contralateral kidney are not well revealed. Inflammation and cell proliferation plays an important role in the process of RIF. Proliferation appears early, even prior to the abnormal deposition of extracellular matrix, and continued throughout the whole process of fibrosis. We hypothesized that aldosterone may induce inflammation and cell proliferation by SGK-1/ NF-κB pathway.Design and method: 36 female Wistar rats weight 200 ± 10 g were used in this study. After 7 days to adapt, rats are randomly divided into 3 groups: Control group, UUO group, and UUO and Eplerenone group. The rats in UUO and Eplerenone group had the UUO operation and treated with Eplerenone of 100 mg/Kg/d. At the tenth day, the serum aldosterone, MCP-1 and TNF-αwere evaluated by radioimmunoassay or ELISA method. The kidneys were harvested for histopathological and biomolecular study. Results: 1 In UUO group, the level of serum aldosterone, MCP-1 and TNF-αwere increased significantly than sham group and they are lowered by Eplerenone. 2 Pathologic changes: in UUO group, severe inflammation can be observed in the contralateral kidneys. Eplerenone treatment decreased the degree of inflammation and interstitial fibrosis in both obstructed and contralateral kidneys. 3 Cell proliferation was examined by PCNA staining and PCNA positive cells increased markedly together with increased collagens in UUO group than control group in contralateral kidney and those changes are attenuated by Elperenone. 4 The expression of SGK-1 protein were upregulated in contralateral kidney in UUO group, which is suppressed by Eplerenone treatment. 5 NF-κB,ERK1/2 and P-ERK1/2 were also increased markedly in contralateral kidney of UUO than Sham group and downregulated after Eplerenone treatment. Conclusions: 1 Cell proliferation in contralateral kidney of UUO may play an important role in the process of RIF. 2 Aldosterone and its receptor (MR) activity are increased in contralateral kidney in obstructive nephropathy and they induce inflammation to stimulate cell proliferation 3 Effect of MR on cell proliferation maybe associated with SGK-1/ NF-κB pathway.
Neisseria gonorrhoeae Isolates with Reduced Susceptibility to Cefixime and Ceftriaxone: Association with Genetic Polymorphisms in penA , mtrR , porB1b , and ponA (2007)

The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced cefixime and ceftriaxone susceptibility (Cef(i)) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cef(i) isolates (n = 18), the MICs of cefixime and ceftriaxone ranged between 0.032 to 0.38 mug/ml and 0.064 to 0.125 mug/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cef(i) isolates (39%), which had somewhat lower MICs of cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to cefixime and ceftriaxone was identified.
The Blood–Brain Barrier and Epilepsy (2006)

During the past several years, there has been increasing interest in the role of the blood-brain barrier (BBB) in epilepsy. Advances in neuroradiology have enhanced our ability to image and study the human cerebrovasculature, and further developments in the research of metabolic deficiencies linked to seizure disorders (e.g., GLUT1 deficiency), neuroinflammation, and multiple drug resistance to antiepileptic drugs (AEDs) have amplified the significance of the BBB's relationship to epilepsy. Prior to 1986, BBB research in epilepsy focused on three main areas: ultrastructural studies, brain glucose availability and transport, and clinical uses of AEDs. However, contrast-based imaging techniques and medical procedures such as BBB disruption provided a framework that demonstrated that the BBB could be reversibly disrupted by pathologic or iatrogenic manipulations, with important implications in terms of CNS drug delivery to "multiple drug resistant" brain. This concept of BBB breakdown for therapeutic purposes has also unveiled a previously unrecognized role for BBB failure as a possible etiologic mechanism in epileptogenesis. Finally, a growing body of evidence has shown that inflammatory mechanisms may participate in the pathological changes observed in epileptic brain, with increasing awareness that blood-borne cells or signals may participate in epileptogenesis by virtue of a leaky BBB. In this article we will review the relationships between BBB function and epilepsy. In particular, we will illustrate consensus and divergence between clinical reality and animal studies.
Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder Cancer (2005)

Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.