gebhart/patrepeval huggingface dataset:
Synthesis of several isotopically labeled pyrrolo[1,3‐d]pyrimidine analogs (2001)

Abstract Four members of a novel class of pyrrolo[2,3‐d]pyrimidines that show potential for the treatment of asthma and neurodegenerative disorders, have been prepared with radioisotope labels and in one case with multiple stable isotope labels for ADME studies as part of the drug development process. The syntheses utilize an isotopically labeled 2,4,6‐trisubstituted pyrimidine as a common building block, readily prepared from isotopically labeled urea. Cyclizations of the pyrimidine with bromo‐ketones generate the ring fused pyrrolo[2,3‐d]‐pyrimidines with elegant efficiency as demonstrated by the preparation of structures 4 , 5 , 8 and 12 . Copyright © 2001 John Wiley &amp; Sons, Ltd.
Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease (2011)

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.
Extended factored space-time processing for airborne radar systems (2003)

Factored space-time processing has been proposed as a reasonable suboptimal solution to reduce ground clutter in an airborne radar system in order to lower the enormous computational complexity required in fully adaptive processing. An algorithm for mitigating loss in performance of the basic factored technique by extending the Doppler filter spatial weight set to include various degrees of adjacent Doppler coupling is described. The extended factored algorithm is developed, and performance results, vis-a-vis the optimal and basic factored approaches, are presented for both theoretical and measured airborne clutter scenarios.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Candida albicans homolog of CDC25 is functional in Saccharomyces cerevisiae (1993)

We have cloned, by functional complementation of the cdc25-2 mutation of Saccharomyces cerevisiae, a homolog of CDC25 from the pathogenic yeast Candida albicans. The new gene, named CSC25 codes for a 1333-amino-acid protein. The full length gene, as well as a truncated form coding for 795 amino acids, suppresses the thermosensitive phenotype of cdc25ts mutants. Biochemical analysis has shown that Csc25 activates the Ras/adenylyl cyclase pathway in S. cerevisiae at a rate two to three times faster than Cdc25, under the same conditions. The C-terminal domain of Csc25 is highly similar to the C-terminal domain of Cdc25, to almost the same extent as the C-terminus of the endogenous Cdc25 homolog Sdc25. We show that polyclonal anti-Cdc25 antibodies interact with Csc25 expressed in S. cerevisiae. In addition to the full length protein (approximately 150 kDa), we have found a approximately 50-kDa polypeptide which seems to include the C-terminus of the CSC25 gene product.
Phase II Evaluation of Lonidamine in Patients with Advanced Malignancy (1984)

Lonidamine, a substituted indazole carboxylic acid with unique effects on cellular respiration, was studied in 27 patients with advanced malignancies. Of the 18 evaluable patients, 5 had small-cell lung cancer, 3 had non-small-cell lung cancer, 3 sarcoma, 2 breast cancer, and 5 other tumour types. All but 1 had had extensive prior treatment. A partial response was seen in 1 patient with metastatic synovial sarcoma, and tumour growth inhibition was demonstrated in 2 other cases. The major toxicity encountered was myalgia (66.6%) which was incompletely ameliorated by prednisone and required dose reduction in 2 patients and cessation of drug in 3. Other toxicities included auditory changes, anorexia, nausea and vomiting, diarrhoea, skin sensitivity, and conjunctivitis. No added toxicity was seen, when Lonidamine was combined with other chemotherapeutic agents. No correlation between Lonidamine dose and serum lactate levels was seen, although 4 patients showed a progressive increase in lactate levels over time, thought to be related to their increasing tumour burden. 5 patients demonstrated a dramatic fall in serum testosterone levels 4-8 weeks after starting Lonidamine which was accompanied by an increase in luteinizing hormone levels in 3 patients. In summary, modest antitumour activity was demonstrated in 3 patients; moderate toxicity was seen in most patients, but was usually tolerable. Further studies of Lonidamine are warranted in less heavily treated patients, alone or in combination with other chemotherapeutic agents.
Thin-Film Microbiosensors for Glucose−Lactate Monitoring (1996)

A miniaturized device for simultaneous measurement of glucose and lactate levels was produced by means of photopatterning of enzyme-containing photosensitive membrane precursors. This device shows no cross-talk and a lifetime for both the glucose and the lactate sensors of more than 2 weeks when continuously operated in undiluted bovine serum. Linear response ranges of up to 40 mM for glucose and 25 mM for L-lactate, in combination with 95% response times of < 30 s, were realized. The devices are mass produced by means of thin-film technology on flexible carriers to give catheter-type multisensing devices for in vivo applications. Ex vivo experiments, performed with human volunteers, where the device was continuously operated in an extracorporeal, undiluted, heparinized blood stream for 6 h, gave a correlation of r > 0.98 with respect to laboratory techniques. Subcutaneous measurements of glucose levels in pigs were close to the corresponding blood levels obtained without in vivo calibration.
Band-gap tuning of InGaAs/InGaAsP/InP laser using high energy ion implantation (1995)

The technique of ion-induced quantum well intermixing using broad area, high energy (1 MeV P+) ion implantation has been used to tune the emission wavelength of an InGaAs/InGaAsP/InP multiple quantum well (MQW) laser operating at 1.5 μm. The optical quality of the band-gap shifted material is assessed using low-temperature photoluminescence (PL). The band-gap tuned lasers are characterized in terms of threshold current density and external quantum efficiency and exhibit blue shifts in the lasing spectra of up to 63 nm. This approach offers the prospect of a powerful and relatively simple fabrication technique for integrating active as well as passive optoelectronic devices.
Multi-point Displacement Response Measurement of Civil Infrastructures Using Digital Image Processing (2011)

In this study, a method to measure multi-point displacement responses by using a digital image processing technique is suggested. Digital images are acquired by a commercial digital camcorder, which is the sensor to measure remote displacement responses considering convenient and economical aspects for use. The digital image correlation (DIC) as one of digital image processing techniques is applied to the algorithm developed and the image transform function (ITF) to correct the movements and errors between the image without deformation and that with deformation is also used to increase the resolution of displacement responses. One shaking table test and several field tests to validate this algorithm, which can measure multi-point displacement responses of structures by using digital image processing techniques, were carried out.
Evaluation of a Novel Technique for Wound Closure Using a Barbed Suture (2006)

The barbed suture represents an innovative option for wound closure. With a cosmesis and safety profile that is similar to that of conventional suture technique, it avoids the drawbacks inherent to suture knots.
Thyroid hormone receptor mutants that cause resistance to thyroid hormone. Evidence for receptor competition for DNA sequences in target genes. (1992)

Several distinct mutations in the ligand-binding domain of the beta form of the thyroid hormone receptor have been reported in kindreds with the autosomal dominant syndrome of generalized resistance to thyroid hormone (GRTH). GRTH receptor mutants are functionally inactive but capable of inhibiting normal receptor function in transient expression studies. We examined the possibility that this dominant negative activity of the GRTH mutants involves competition for receptor binding to DNA. Mutations introduced into either the T3 ligand-binding domain (LBD) or into the DNA-binding domain (DBD) of the receptor eliminated the transcriptional activity of the receptor. In cotransfection experiments, the LBD mutants, but not the DBD mutants, inhibited the transcriptional activity of the normal receptor. The inhibitory activity of the LBD mutants was abolished by the introduction of an additional mutation into the DBD, suggesting that the DBD is required for dominant negative activity. A chimeric receptor, in which the DNA-binding domain of the thyroid hormone receptor was exchanged with the homologous region in the glucocorticoid receptor (GTG), was used to study thyroid hormone receptor competition for GTG interactions with thyroid receptor target sequences. In the absence of thyroid hormone, the normal thyroid hormone receptor inhibited dexamethasone stimulated transcription by GTG. The transcriptional activity of GTG was also inhibited by the LBD mutants but not by a DBD mutant of the thyroid hormone receptor. These results indicate that the thyroid hormone receptor mutations that occur in GRTH compete with normal receptors at DNA-binding sites in target genes to block normal receptor function.
Performance of the VAX-11/780 translation buffer (1985)

A virtual-address translation buffer (TB) is a hardware cache of recently used virtual-to-physical address mappings. The authors present the results of a set of measurements and simulations of translation buffer performance in the VAX-11/780. Two different hardware monitors were attached to VAX-11/780 computers, and translation buffer behavior was measured. Measurements were made under normal time-sharing use and while running reproducible synthetic time-sharing work loads. Reported measurements include the miss ratios of data and instruction references, the rate of TB invalidations due to context switches, and the amount of time taken to service TB misses. Additional hardware measurements were made with half the TB disabled. Trace-driven simulations of several programs were also run; the traces captured system activity as well as user-mode execution. Several variants of the 11/780 TB structure were simulated.
Efficient hybrid organic-inorganic light emitting diodes with self-assembled dipole molecule deposited metal oxides (2010)

We investigate the effect of self-assembled dipole molecules (SADMs) on ZnO surface in hybrid organic-inorganic polymeric light-emitting diodes (HyPLEDs). Despite the SADM being extremely thin, the magnitude and orientation of SADM dipole moment effectively influenced the work function of the ZnO. As a consequence, the charge injection barrier between the conduction band of the ZnO and the lowest unoccupied molecular orbital of poly(9,9′-dioctylfluorene)-co-benzothiadiazole could be efficiently controlled resulting that electron injection efficiency is remarkably enhanced. The HyPLEDs modified with a negative dipolar SADM exhibited enhanced device performances, which correspond to approximately a fourfold compared to those of unmodified HyPLEDs.
Detection of Lipid Pool, Thin Fibrous Cap, and Inflammatory Cells in Human Aortic Atherosclerotic Plaques by Near-Infrared Spectroscopy (2002)

NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients.
Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: A potential clinical marker and mediator of severe sepsis* (2007)

Inter-alpha inhibitor proteins are markedly reduced in severe sepsis, and failure of recovery of IalphaIp levels over the course of sepsis is associated with an unfavorable outcome.
Mental stress--induced myocardial ischemia and cardiac events (1996)

The presence of mental stress-induced ischemia is associated with significantly higher rates of subsequent fatal and nonfatal cardiac events, independent of age, baseline LVEF, and previous myocardial infarction, and predicted events over and above exercise-induced ischemia. These data suggest that the relationship between psychological stress and adverse cardiac events may be mediated by the occurrence of myocardial ischemia.
Information Management: A Proposal (1990)

This proposal concerns the management of general information about accelerators and experiments at CERN.It discusses the problems of loss of information about complex evolving systems and derives a solution based on a distributed hypertext system.
Transfer RNA Modulates the Editing Mechanism Used by Class II Prolyl-tRNA Synthetase (2008)

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs. To prevent errors in protein synthesis, many synthetases have evolved editing pathways by which misactivated amino acids (pre-transfer editing) and misacylated tRNAs (post-transfer editing) are hydrolyzed. Previous studies have shown that class II prolyl-tRNA synthetase (ProRS) possesses both pre- and post-transfer editing functions against noncognate alanine. To assess the relative contributions of pre- and post-transfer editing, presented herein are kinetic studies of an Escherichia coli ProRS mutant in which post-transfer editing is selectively inactivated, effectively isolating the pre-transfer editing pathway. When post-transfer editing is abolished, substantial levels of alanine mischarging are observed under saturating amino acid conditions, indicating that pre-transfer editing alone cannot prevent the formation of Ala-tRNA Pro. Steady-state kinetic parameters for aminoacylation measured under these conditions reveal that the preference for proline over alanine is 2000-fold, which is well within the regime where editing is required. Simultaneous measurement of AMP and Ala-tRNA Pro formation in the presence of tRNA Pro suggested that misactivated alanine is efficiently transferred to tRNA to form the mischarged product. In the absence of tRNA, enzyme-catalyzed Ala-AMP hydrolysis is the dominant form of editing, with "selective release" of noncognate adenylate from the active site constituting a minor pathway. Studies with human and Methanococcus jannaschii ProRS, which lack a post-transfer editing domain, suggest that enzymatic pre-transfer editing occurs within the aminoacylation active site. Taken together, the results reported herein illustrate how both pre- and post-transfer editing pathways work in concert to ensure accurate aminoacylation by ProRS.
Wetting of Regularly Structured Gold Surfaces (2005)

In this study we report results for a systematic study of the wetting of structured gold surfaces formed by electrodeposition through monolayer templates of close-packed uniform submicrometer spheres. Removal of the template after deposition leaves a regular hexagonal array of sphere segment pores where the depth of the pores and, thus, the topography of the surface are controlled by the thickness of gold deposited through the template. We find that, as the thickness of the porous film increases up to the radius of the pores, the apparent contact angle for water on the surface increases from 70 degrees on the flat surface to more that 130 degrees , and then with increasing thickness above the radius of the pores the apparent contact angle decreases back toward 70 degrees . We show that these changes in the apparent contact angle agree with the model of Cassie and Baxter for nonwetted surfaces even though the gold itself is hydrophilic. We also show that the apparent contact angle is independent of the diameter of the pores over the range 400-800 nm. This is the first reported example showing the change of a hydrophilic surface (theta; < 90 degrees ) into a hydrophobic surface (theta; > 90 degrees ) purely by control of the surface topography. The role of the pore shape and size in stabilizing the nonwetting (Cassie-Baxter) droplet on the surface is discussed.
SEED BACTERIAL ENDOPHYTES: COMMON GENERA, SEED-TO-SEED VARIABILITY AND THEIR POSSIBLE ROLE IN PLANTS (2012)

ISHS XXVIII International Horticultural Congress on Science and Horticulture for People (IHC2010): International Symposium on Environmental, Edaphic, and Genetic Factors Affecting Plants, Seeds and Turfgrass SEED BACTERIAL ENDOPHYTES: COMMON GENERA, SEED-TO-SEED VARIABILITY AND THEIR POSSIBLE ROLE IN PLANTS
Alignment Control in Holographic Polymer Dispersed Liquid Crystal. (2000)

Alignment control is promising approach for improving the characteristics of holographic polymer dispersed liquid crystal (HPDLC). This paper describes the methods of controlling the alignment of LC molecules in HPDLC (by using an electric field, shear force, and LC monomer) and the resulting characteristics of the devices. When the alignment is controlled, the diffraction characteristics can have polarization selectivity. The diffraction efficiency is also improved, because the optical anisotropy of LC molecules can be fully used.
Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and angiogenic activity in human endothelial cells (2014)

Cyclo[DKP-RGD] 1 can be a potential modulator of angiogenesis induced by different growth factors, possibly devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.
R2* imaging of transfusional iron burden at 3T and comparison with 1.5T (2007)

These preliminary data suggest that the iron-dependent component of R2* scales linearly with field strength over a wide range of tissue iron concentrations. The incidence of susceptibility artifacts may, however, also increase with field strength.
Painful Research: Identification of a Small-Molecule Inhibitor that Selectively Targets Nav1.8 Sodium Channels (2007)

Voltage-gated sodium channels in nociceptive neurons are attractive targets for novel pain therapeutics. Although drugs that target voltage-gated sodium channels have proven value as pain therapeutics, the drugs that are currently available are non-specific sodium channel inhibitors, which limit their usefulness. Recently, a selective small-molecule inhibitor of Na(v)1.8, a voltage-gated sodium channel isoform that participates in peripheral pain mechanisms, has been developed. This exciting new compound shows efficacy in several animal models of pain and is anticipated to be only the first of many new isoform-specific sodium channel blockers.
ProbCons: Probabilistic consistency-based multiple sequence alignment (2005)

To study gene evolution across a wide range of organisms, biologists need accurate tools for multiple sequence alignment of protein families. Obtaining accurate alignments, however, is a difficult computational problem because of not only the high computational cost but also the lack of proper objective functions for measuring alignment quality. In this paper, we introduce probabilistic consistency, a novel scoring function for multiple sequence comparisons. We present ProbCons, a practical tool for progressive protein multiple sequence alignment based on probabilistic consistency, and evaluate its performance on several standard alignment benchmark data sets. On the BAliBASE, SABmark, and PREFAB benchmark alignment databases, ProbCons achieves statistically significant improvement over other leading methods while maintaining practical speed. ProbCons is publicly available as a Web resource.
Crosslinking of fluoroelastomers by “click” azide-nitrile cycloaddition (2015)

A fluoroelastomer that bears pendant nitrile groups is crosslinked with a telechelic bis-azido fluorinated curing agent by “click” azide–nitrile cycloaddition. Thermogravimetric analyses of the resulting press cured films reveal an improvement by 20 °C of the thermal degradation profile under air, compared to that of the corresponding uncured fluoroelastomer. Additional Supporting Information may be found in the online version of this article. Supplementary Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Rare‐Earth Barium Stannates: Synthesis, Characterization, and Potential Use as Substrates for YBa 2 Cu 3 O 7‐δ Superconductor (1995)

A new group of complex perovskites, REBa 2 SnO 5.5 (where RE = Pr, Sm, Eu, and Gd) have been synthesized and sintered as single‐phase materials with high sintered density and stability by the solid‐state reaction method. The structure of REBa 2 SnO 5.5 was studied by the X‐ray diffraction technique, and all of them were found to be isostructural and have a cubic perovskite structure. The dielectric constant and loss factor values of these materials are in a range suitable for substrate applications. The X‐ray diffraction and resistivity measurements have shown that there is no detectable reaction between YBa 2 Cu 3 O 7‐δ and REBa 2 SnO 5.5 , even when the substances are mixed thoroughly and sintered at 950°C for 15 h. Thick films of YBa 2 Cu 3 O 7‐δ fabricated on polycrystalline REBa 2 SnO 5.5 substrates gave superconducting zero resistivity transition T C(0) = 92 K, indicating the suitability of these new materials as substrates for YBa 2 Cu 3 O 7‐δ films.
Azasteroids: structure-activity relationships for inhibition of 5.alpha.-reductase and of androgen receptor binding (1986)

A series of steroids, primarily 4-azasteroids, were prepared and tested in vitro as inhibitors of human and rat prostatic 5 alpha-reductase and of binding of dihydrotestosterone to the rat androgen receptor. The primary structural modifications were changes of the A ring and of moieties attached at the C-17 position of the steroid nucleus. New A-ring modifications included the 4-cyano-3-oxo-delta 4 system in the carbocyclic series and 1 alpha-CN, 1 alpha-CH3, 1 alpha,2 alpha-CH2, 2 beta-F, 2-aza, 2-oxa, and A-homo changes in the 3-oxo-4-aza series. In addition, 4-azasteroids with a D-homo ring or methyl substitution at C-7 (alpha and beta) or C-16 (alpha and beta) were prepared. The majority of the C-17 substituents were prepared from reactive intermediates derived from the 17 beta-COOH. Enhanced 5 alpha-reductase inhibition in both the human and rat enzyme assays is seen with 4-CN substitution on 3-oxo-delta 4 steroids and with a C-17 side chain incorporating a lipophilically substituted semipolar group on the 4-aza-3-oxo-5 alpha-androstane nucleus. Fewer highly active compounds were found in the human enzyme assay than in the rat assay. Structural requirements for inhibition of the rat androgen receptor are much different from those for inhibition of the enzyme. The 17 beta-OH moiety enhances potency more than any other feature while introduction of double bonds at C-1 or C-5 in the azasteroid gives a small improvement. Azasteroids unsubstituted at the 4-position show greatly diminished receptor activity.
Adenovirus-mediated soluble FLT-1 gene therapy for ovarian carcinoma. (2001)

Our results suggest that adenovirus-mediated sFLT-1 gene therapy can effectively inhibit ovarian tumor growth and increase survival in a murine model of ovarian carcinoma.