gebhart/patrepeval huggingface dataset:
Soluble 2-Substituted Aminopyrido[2,3-d]pyrimidin-7-yl Ureas. Structure−Activity Relationships against Selected Tyrosine Kinases and Exploration of in Vitro and in Vivo Anticancer Activity (2001)

In continuing our search for medicinal agents to treat proliferative diseases, we have discovered 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas as a novel class of soluble, potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 1, several series of analogues were made that examined the C-6 aryl substituent, a variety of water solublizing substitutents at the C-2 position, and urea or other acyl functionality at the N-7 position. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr;) and nonreceptor (c-Src) classes. Several of the most potent compounds displayed submicromolar inhibition of PDGF-mediated receptor autophosphorylation in rat aortic vascular smooth muscle cells and low micromolar inhibition of cellular growth in five human tumor cell lines. One of the more thoroughly evaluated members, 32, with IC50 values of 0.21 microM (PDGFr), 0.049 microM (bFGFr), and 0.018 microM (c-Src), was evaluated in in vivo studies against a panel of five human tumor xenografts, with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs. Compound 32 produced a tumor growth delay of 14 days against the Colo-205 colon xenograft model.
A new ferredoxin-dependent carbon reduction cycle in a photosynthetic bacterium. (1966)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Expression of altered α2-adrenergic phenotypic traits in normotensive humans at genetic risk of hereditary (essential) hypertension (1998)

We conclude that heterogeneous, bimodally distributed hemodynamic responses to alpha2-adrenergic blockade in subjects with positive family histories of hypertension suggest a discrete subgroup with early expression of perhaps Mendelian traits associated with risk of later development of hypertension. Such phenotypic traits ('intermediate phenotypes'), with earlier penetrance than hypertension itself, can be
Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database (2010)

Here, we present the algorithm and validation for OMEGA, a systematic, knowledge-based conformer generator. The algorithm consists of three phases: assembly of an initial 3D structure from a library of fragments; exhaustive enumeration of all rotatable torsions using values drawn from a knowledge-based list of angles, thereby generating a large set of conformations; and sampling of this set by geometric and energy criteria. Validation of conformer generators like OMEGA has often been undertaken by comparing computed conformer sets to experimental molecular conformations from crystallography, usually from the Protein Databank (PDB). Such an approach is fraught with difficulty due to the systematic problems with small molecule structures in the PDB. Methods are presented to identify a diverse set of small molecule structures from cocomplexes in the PDB that has maximal reliability. A challenging set of 197 high quality, carefully selected ligand structures from well-solved models was obtained using these methods. This set will provide a sound basis for comparison and validation of conformer generators in the future. Validation results from this set are compared to the results using structures of a set of druglike molecules extracted from the Cambridge Structural Database (CSD). OMEGA is found to perform very well in reproducing the crystallographic conformations from both these data sets using two complementary metrics of success.
Cell-Free Circulating DNA: Diagnostic Value in Patients With Testicular Germ Cell Cancer (2008)

Cell-free DNA levels are increased in patients with testicular cancer and they allow the accurate discrimination of healthy individuals. The high sensitivity of cell-free DNA could facilitate the management of testicular cancer, especially in patients with conventional tumor markers that are not increased.
TGF- β Promotes the Growth of Bovine Chondrocytes in Monolayer Culture and the Formation of Cartilage Tissue on Three-Dimensional Scaffolds (1995)

We have investigated the ability of transforming growth factor beta (TGF-beta) to promote the growth and differentiation of chondrocytes in monolayer and on three-dimensional scaffolds. Treatment of chondrocytes with TGF-beta and ascorbate individually stimulated the proliferation of bovine articular chondrocytes about 2-fold when cells were grown in monolayer culture: the combination of TGF-beta and ascorbate resulted in a 3-fold increase in cell number over a 72-h period. Peak stimulation with TGF-beta occurred at about 1.0 ng/ml: bFGF was slightly inhibitory in these assays. TGF-beta led to an increase in glycosaminoglycan synthesis as detected by Western blotting using anti-chondroitin sulfate antibodies. No significant change in collagen type II mRNA or protein was observed. When cells were grown on grown on three-dimensional scaffolds composed of polyglyocolic acid, TGF-beta treatment led to an increase in the size of the cartilage-like constructs produced. This was accompanied by increases in collagen and glycosaminoglycan deposition; immunohistochemical staining showed that the predominant collagen was type II. These results indicate that TGF-beta is capable of increasing the proliferation rate of chondrocytes in monolayer as well as increasing cartilage production on three-dimensional scaffolds and may find utility in the in vitro engineering of cartilage tissue.
Novel Design of Nonpeptide AVP V2Receptor Agonists:  Structural Requirements for an Agonist Having 1-(4-Aminobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine as a Template (2000)

The discovery of a series of nonpeptide arginine vasopressin V(2) receptor agonists is described. After identifying the aniline derivative 8 as our lead compound from the metabolites of compound 7 that showed antidiuretic activity by po administration to Brattleboro rats, improvements in the in vitro potency involving evaluations of the structural requirements for agonist action and optimizing the structure of the benzoyl moiety have been intensively undertaken. These studies led to compounds 16g, 19a, and 23b,h,i that show potent agonist activity for the V(2) receptor.
Characterization of sulfation patterns of beef and pig mucosal heparins by nuclear magnetic resonance spectroscopy. (1996)

Though differing only slightly in their degrees of sulfation, heparin preparations from pig mucosa and those from beef mucosa have consistently different 13C- and 1H-NMR spectra, which provide useful fingerprints for distinguishing the two types of heparin. Integrated areas of NMR signals associated with minor, undersulfated sequences (assigned by comparison with mono-dimensional spectra of selectively desulfated heparins and by analysis of two-dimensional spectra of heparins prepared from pig and beef mucosa) permit quantitation of differences in sulfation patterns. Undersulfation of pig mucosal heparins at position 6 of the hexosamine units, determined by 13C-NMR and expressed as percent glucosamines nonsulfated at C6 referred to total glucosamines, is substantially lower for pig mucosal heparins than for beef mucosal heparins (16.9-21.7% vs 36.7-40.7%; average values: 18.6% vs 40.3%). By contrast, undersulfation at position 2 of the iduronic acid units, determined by 1H-NMR and expressed as percent nonsulfated iduronic acid referred to total (sulfated + nonsulfated) iduronic acid is significantly higher for pig mucosal preparations (9.6-13.5% vs 2.1-2.7%; average values: 12.7% vs 2.3%). Pig mucosal heparins also have a significantly higher content of 3-O-sulfated glucosamine units, which are markers for the active site of heparin for antithrombin-III.
Loss of annexin 1 correlates with early onset of tumorigenesis in esophageal and prostate carcinoma. (2000)

Annexin I protein expression was evaluated in patient-matched longitudinal study sets of laser capture microdissected normal, premalignant, and invasive epithelium from human esophageal squamous cell cancer and prostatic adenocarcinoma. In 25 esophageal cases (20 by Western blot and 5 by immunohistochemistry) and 17 prostate cases (3 by Western blot and 14 by immunohistochemistry), both tumor types showed either complete loss or a dramatic reduction in the level of annexin I protein expression compared with patient-matched normal epithelium (P < or = 0.05). Moreover, by using Western blot analysis of laser capture microdissected, patient-matched longitudinal study sets of both tumor types, the loss of protein expression occurred in premalignant lesions. Concordance of this result with immunohistochemical analysis suggests that annexin I may be an essential component for maintenance of the normal epithelial phenotype. Additional studies investigating the mechanism(s) and functional consequences of annexin I protein loss in tumor cells are warranted.
Mda‐7/IL‐24 induces apoptosis of diverse cancer cell lines through JAK/STAT‐independent pathways (2003)

Experimental evidence documents that the MDA-7/IL-24 protein (an IL-10 family cytokine) binds to IL-20 and IL-22 receptor complexes resulting in the activation of JAK/STAT signaling pathways. Recent published reports utilizing human blood derived primary lymphocytes have provided additional confirmatory evidence relating to the cytokine properties of this molecule. A notable attribute of mda-7/IL-24 is its cancer cell-specific apoptosis inducing capacity, which currently remains incompletely understood. Treatment with distinctive tyrosine kinase inhibitors (Genistein and AG18) or a JAK-selective inhibitor (AG490) did not prevent Ad.mda-7 induced apoptosis in diverse cell lines. In addition, there is no apparent correlation between patterns of expression of IL-20R1, IL-20R2, and IL-22R mRNA and susceptibility to Ad.mda-7 in different cell lines. Furthermore, Ad.mda-7 is able to induce killing in STAT/JAK deficient cells. In contrast, treatment with the p38(MAPK) selective inhibitor SB203580, partially inhibited apoptosis induced by Ad.mda-7 in different cell lines. These results demonstrate for the first time that signaling events leading to susceptibility to Ad.mda-7 induced apoptosis, might be tyrosine kinase independent and can thus be distinguished from its cytokine function related properties mediated by the IL-20/IL-22 receptor complexes that require JAK/STAT kinase activity.
Real-time production scheduling in a multi-purpose batch-oriented environment (1993)

The chemical company Omnichem has plants in Wetteren, Balen and Louvain-la-Neuve in Belgium. It has implemented an automated real-time batch-oriented scheduling procedure, in the first place for its synthesis plants on the Wetteren site. A constraint-based solution was chosen, taking into account the great number of rules and restrictions and the need to change the optimisation criterion when necessary (e,g. for just-in-time procedures). Within this context, interactive communication with the planner via a graphical user interface was absolutely essential. To guarantee a planning module that could meet Omnichem's requirements in a complex batch-oriented production environment, special features were employed such as artificial intelligence to guide the planner, an object-oriented database, interfaces with material requirement planning and process control, and flexible interaction with the scheduling system. This article outlines the definition of the problem, describes the design criteria for an automated real-time batch-oriented scheduler, and discusses the procedure followed to reach a solution. A short description is also included of the scheduling system actually implemented.
<title>High-performance liquid crystal device suitable for projection display</title> (1996)

We report progress to develop a miniature reflective display with a silicon backplane that can be used to project full color video images. This display has sufficient speed for sequential color at full video rates. It can tolerate the high light flux levels required for projecting bright images. The display has more than 640 X 480 pixels on a 20 micron pitch. Each pixel is an 18 micron square mirror. The mirror surface can be either overcoated aluminum or a high efficiency dielectric mirror.
On the Sum-Rate of Multiuser MIMO Uplink Channels with Jointly-Correlated Rician Fading (2011)

In this paper, we study the capacity-achieving input covariance matrices for the multiuser multiple-input multiple-output (MIMO) uplink channel under jointly-correlated Rician fading when perfect channel state information (CSI) is known at the receiver, or CSIR while only statistical CSI at the transmitter, or CSIT, is available. The jointly-correlated MIMO channel (or the Weichselberger model) accounts for the correlation at two link ends and is shown to be highly accurate to model real channels. Classically, numerical techniques together with Monte-Carlo methods (named stochastic programming) are used to resolve the problem concerned but at a high computational cost. To tackle this, we derive the asymptotic sum-rate of the multiuser (MU) MIMO uplink channel in the large-system regime where the numbers of antennas at the transmitters and the receiver go to infinity with constant ratios. Several insights are gained from the analytic asymptotic sum-rate expression, based on which an efficient optimization algorithm is further proposed to obtain the capacity-achieving input covariance matrices. Simulation results demonstrate that even for a moderate number of antennas at each link, the new approach provides indistinguishable results as those obtained by the complex stochastic programming approach.
The Effect of Estradiol Vaginal Tablet and Conjugated Estrogen Cream on Urogenital Symptoms in Postmenopausal Women: A Comparative Study (2001)

Estradiol vaginal tablet and conjugated estrogen cream were effective in treating urogenital symptoms, the restoration of normal vaginal epithelium and reduction of vaginal pH in postmenopausal women. However, 2 cases of endometrial proliferation were noted.
Surface Patterning Using Self Assembled Monolayers (SAMs) (2010)

Self Assembled Monolayers (SAMs) are nanostructures and are a fundamental component of nanoscience and nanotechnology. SAMs are a preferred tool for carrying out surface modification of a variety of materials and are a subject of widespread scientific attention across many disciplines. The ability to tailor the physical, mechanical as well as the chemical properties of the final substrate has placed SAMs in a unique position in materials science and surface chemistry in particular. Patterning of a SAM is an important step as secondary modification which further enhances the feasibility of SAMs for specific solutions to many problems in nanoscience. Here we present a brief introduction to the subject of SAM patterning by providing an introduction to the concept of a Self Assembled Monolayer (SAM) followed by a brief review of mixed SAMs. After this, the various strategies and techniques available for patterning SAMs are presented and some of their potential biomedical applications discussed.
Diagnosis of Ebola haemorrhagic fever by RT-PCR in an epidemic setting (2000)

This study reports the first field evaluation of a new diagnostic technique for Ebola virus disease with sensitivity and specificity. Ebola virus causes rare but fulminating outbreaks in Equatorial Africa. Rapid differentiation from other infections is critical for timely implementation of public health measures. Patients usually die before developing antibodies, necessitating rapid virus detection. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed, implemented and evaluated at Centre International de Recherches Médicales de Franceville (CIRMF) in Gabon, to detect Ebola viral RNA in peripheral blood mononuclear cells (PBMC). Twenty-six laboratory-confirmed patients during and 5 after the acute phase of Ebola haemorrhagic fever, 15 healthy controls and 20 febrile patients not infected with Ebola virus were studied. RT-PCR results were compared with ELISA antigen capture, and Ebola specific IgM and IgG antibody detection. Ebola virus RNA was amplified from 26/26 specimens from the acute phase, 3/5 during recovery, 0/20 febrile patients and 1/15 negative controls. Sensitivity of RT-PCR in identifying acute infection and early convalescence compared with antigen or IgM detection was 100% and 91% respectively, and specificity compared with antigen detection and IgM assay combined was 97%. Antigen capture detected only 83% of those identified by PCR, and IgM only 67%. Ebola virus RNA was detected in all 13 fatalities, only 5 of whom had IgM and none IgG. RT-PCR detected Ebola RNA in PBMC one to three weeks after disappearance of symptoms when antigen was undetectable. RT-PCR was the most sensitive method and able to detect virus from early acute disease throughout early recovery.
Handbook of semiconductor wafer cleaning technology : science, technology, and applications (1994)

The cleaning of semiconductor wafers has become one of the most critical operations in the fabrication of semiconductor devices. The considerable body of technical and scientific literature is widely dispersed in numerous journals and symposia proceedings. This book brings together in one volume all pertinent knowledge on semiconductor wafer cleaning and its associated scientific and technical disciplines. It provides the first comprehensive and up-to-date coverage of this rapidly evolving field
Piezoelectricity in cellular electret films (2000)

Permanently charged films with a cellular or porous structure represent a new family of polymer electrets. These materials show piezoelectric properties with high piezoelectric constants. The electromechanical response equations of such films are derived for their operation as sensors and as actuators. Experimental results are also presented for cellular polypropylene (pp). In particular, measurements of the direct and inverse piezoelectric constants in the frequency range 0 to 10 kHz and of the variation of these constants across the surface of the films are discussed. These measurements, performed by direct application of stress or by the use of a profilometer, an accelerometer and an interferometer yield a frequency-independent piezoelectric d/sub 33/ constant of /spl lsim/ 220 pC/N. Assuming reasonable charge distributions and charge densities, the calculated piezoelectric constants are in good agreement with the measured values. The theoretical model shows the reciprocity of the piezoelectric constants.
A Novel α-Ketoglutaric Semialdehyde Dehydrogenase (2006)

Azospirillum brasilense possesses an alternative pathway of l-arabinose metabolism, which is different from the known bacterial and fungal pathways. In a previous paper (Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 2612-2623), we identified and characterized l-arabinose 1-dehydrogenase, which catalyzes the first reaction step in this pathway, and we cloned the corresponding gene. Here we focused on the fifth enzyme, alpha-ketoglutaric semialdehyde (alphaKGSA) dehydrogenase, catalyzing the conversion of alphaKGSA to alpha-ketoglutarate. alphaKGSA dehydrogenase was purified tentatively as a NAD(+)-preferring aldehyde dehydrogenase (ALDH) with high activity for glutaraldehyde. The gene encoding this enzyme was cloned and shown to be located on the genome of A. brasilense separately from a gene cluster containing the l-arabinose 1-dehydrogenase gene, in contrast with Burkholderia thailandensis in which both genes are located in the same gene cluster. Higher catalytic efficiency of ALDH was found with alphaKGSA and succinic semialdehyde among the tested aldehyde substrates. In zymogram staining analysis with the cell-free extract, a single active band was found at the same position as the purified enzyme. Furthermore, a disruptant of the gene did not grow on l-arabinose. These results indicated that this ALDH gene was the only gene of the NAD(+)-preferring alphaKGSA dehydrogenase in A. brasilense. In the phylogenetic tree of the ALDH family, alphaKGSA dehydrogenase from A. brasilense falls into the succinic semialdehyde dehydrogenase (SSALDH) subfamily. Several putative alphaKGSA dehydrogenases from other bacteria belong to a different ALDH subfamily from SSALDH, suggesting strongly that their substrate specificities for alphaKGSA are acquired independently during the evolutionary stage. This is the first evidence of unique "convergent evolution" in the ALDH family.
Methods and theory for analysis of flow of white cell subpopulations through micropore filters (1988)

Methods have been developed for analysing the resistance of WBC to flow, by measuring their transit rates through 5 and 8 microns pore filters at constant pressure. Unfractionated WBC and separated subpopulations have been compared. For either pore size, lymphocytes exhibited least resistance to flow, followed by granulocytes, with monocytes being most resistant. A theoretical model, which represents WBC suspensions as made up of three particle types (a relatively fast and a relatively slow population, plus a pore blocking population) adequately describes the data for flow rate versus volume filtered. For 5 microns pores, this theory indicates that a majority of WBC have transit times approximately less than 0.5 s. Unfractionated and mixed mononuclear samples contained a proportion of particles with transit times an order of magnitude longer, whereas, for granulocytes, no slow flowing population was evident. Removal of monocytes by plating out, reduced the proportion of the slow particles in the mononuclear preparation. Unique values for transit times could not be determined for 8 microns pores, but it could be concluded that the great majority of WBC made a very quick transit, with the flow becoming dominated by a small number of much more resistant cells. Simple flow parameters (initial relative flow rate and slow particle resistance) are described which characterize these two populations. Both 5 and 8 microns pore data indicated that few cells became permanently trapped within pores.