gebhart/patrepeval huggingface dataset:
Sub‐100 nm, Centimeter‐Scale, Parallel Dip‐Pen Nanolithography (2005)

Atomic force microscope (AFM) cantilever linear arrays are used for parallel dip-pen nanolithography (DPN). Three different tip configurations are studied, all of which involve only a single feedback system in a conventional AFM instrument or an Nscriptor, a dedicated instrument designed for DPN. A simple and convenient tip–substrate alignment procedure provides centimeter-scale, sub-100 nm resolution patterning (see micrograph image). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2421/2005/z500202_s.pdf or from the author. 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.
Aurora Kinases as Anticancer Drug Targets (2008)

Abstract The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. The expression of aurora C in cancer is less well studied. In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. Preliminary clinical data from phase I trials have largely been consistent with cytostatic effects, with disease stabilization as the best response achieved in solid tumors. Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.
Inhibition of Translation by mRNA Encoding NIPP‐1, a Nuclear Inhibitor of Protein Phosphatase‐1 (1997)

Transient transfection of COS-1 cells with an expression vector for NIPP-1, a nuclear subunit of protein phosphatase-1, did not result in an overexpression of NIPP-1 protein, although the levels of mRNA encoding NIPP-1 increased dramatically. Moreover, high concentrations of NIPP-1 mRNA inhibited the translation in reticulocyte lysates of various unrelated mRNAs. This inhibition of translation was caused by the NIPP-1 messenger and not by the translation product, since mutation of the start codon abolished NIPP-1 protein production, but had no influence on the translational inhibition. Analysis of deletion mutants showed that the inhibition was mediated by a 0.5-kb fragment in the 5'-end of the NIPP-1 mRNA. This region, when inserted in the 5'-untranslated region of the beta-galactosidase messenger, inhibited the translation of beta-galactosidase mRNA in COS-1 cells. A predicted highly stable secondary structure deltaG = -239.5 kJ/mol) is present between residues 300 and 500 of NIPP-1 mRNA. The possible importance of this structure in the translational inhibition is discussed.
Neuronal Injury Associated with HIV-1 and Potential Treatment with Calcium-Channel and NMDA Antagonists (1994)

A substantial number of adults and half of the children with acquired immunodeficiency syndrome (AIDS) suffer from neurological manifestations. Among the various pathologies reported in brains of patients with AIDS is neuronal injury and loss, although neurons themselves do not appear to be infected by HIV-1. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells, especially after interacting with astrocytes, secrete neurotoxic substances. Not all of these substances are yet known, but they may include eicosanoids, platelet-activating factor, quinolinate, cysteine, cytokines, and free radicals. Macrophages activated by HIV-1 envelope protein gp120 also appear to release similar toxins. Some of these factors can lead to increased glutamate release or decreased glutamate reuptake. A final common pathway for neuronal suceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-asparate (NMDA) receptor-operated channels, and therefore offers hope for future pharmacological intervention. This review focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future.
Multiplex Analysis of Heterophil Antibodies in Patients With Indeterminate HIV Immunoassay Results (2001)

We hypothesized that heterophil antibodies reactive with animal proteins used in blot preparation caused nonspecific staining (NSS) on HIV Western blot (WB) studies, causing indeterminate results. We analyzed samples showing NSS on HIV WB using a multiplexed immunoassay to simultaneously measure IgG antibodies to animal IgG (bovine, goat, sheep, mouse) and bovine serum albumin. Heterophil antibodies reactive with IgG from several animal species were detected in 23 (49%) of 47 samples showing NSS on HIV WB; 15 positive samples demonstrated antibodies to all 5 antigens. Similar IgG heterophil antibodies were detected in only 2 (8%) of 24 control samples. Of the HIV WB samples with a positive HIV-1 enzyme-linked immunosorbent assay (ELISA) result at the time of WB testing (11/47), heterophil antibodies were found in 8 (73%) of 11. Preabsorption with bovine, goat, and sheep IgG removed heterophil antibodies detected by the multiplexed assay and, in some cases, eliminated reactivity in ELISA and WB testing. Heterophil antibodies are associated with indeterminate HIV immunoassay results and are an important cause of false-positive HIV ELISA results. Multiplexed immunoassays provide a powerful tool for screening patients for heterophil antibodies and resolving possible false-positive results.
Increased expression of angiogenic growth factors in age-related maculopathy (1997)

These results demonstrate an increased expression of VEGF in the RPE, and in the outer nuclear layer in maculae with ARM, that could be involved in the pathogenesis of neovascular macular degeneration. Furthermore, enhanced TGF-beta expression in the RPE cells of maculae with early stages of ARM was shown.
Design of a Mechanism‐Based Probe for Neuraminidase To Capture Influenza Viruses (2005)

Getting a grip on the flu: A mechanism-based probe, 1, for neuraminidase was developed. It is capable of forming a biotinylated adduct with neuraminidase (NA) from Arthrobacter ureafaciens. It also displays an inhibitory effect on a number of NA activities. ELISA experiments successfully demonstrated that influenza viruses can be selectively captured with this probe. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z501738_s.pdf or from the author. 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.
Using Accelerometer and Gyroscopic Measures to Quantify Postural Stability (2015)

The iPad2 hardware provided data of sufficient precision and accuracy to quantify postural stability. Accuracy, portability, and affordability make using the iPad2 a reasonable approach for assessing postural stability in clinical and field environments.
Plant-derived 3,3′-Diindolylmethane Is a Strong Androgen Antagonist in Human Prostate Cancer Cells (2003)

3,3'-Diindolylmethane (DIM) is a major digestive product of indole-3-carbinol, a potential anticancer component of cruciferous vegetables. Our results indicate that DIM exhibits potent antiproliferative and antiandrogenic properties in androgen-dependent human prostate cancer cells. DIM suppresses cell proliferation of LNCaP cells and inhibits dihydrotestosterone (DHT) stimulation of DNA synthesis. These activities were not produced in androgen-independent PC-3 cells. Moreover, DIM inhibited endogenous PSA transcription and reduced intracellular and secreted PSA protein levels induced by DHT in LNCaP cells. Also, DIM inhibited, in a concentration-dependent manner, the DHT-induced expression of a prostate-specific antigen promoter-regulated reporter gene construct in transiently transfected LNCaP cells. Similar effects of DIM were observed in PC-3 cells only when these cells were co-transfected with a wild-type androgen receptor expression plasmid. Using fluorescence imaging with green fluorescent protein androgen receptor and Western blot analysis, we demonstrated that DIM inhibited androgen-induced androgen receptor (AR) translocation into the nucleus. Results of receptor binding assays indicated further that DIM is a strong competitive inhibitor of DHT binding to the AR. Results of structural modeling studies showed that DIM is remarkably similar in conformational geometry and surface charge distribution to an established synthetic AR antagonist, although the atomic compositions of the two substances are quite different. Taken together with our published reports of the estrogen agonist activities of DIM, the present results establish DIM as a unique bifunctional hormone disrupter. To our knowledge, DIM is the first example of a pure androgen receptor antagonist from plants.
Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor. (1988)

The 27-amino-acid gastrin-releasing peptide (GRP1-27) is a neuropeptide and growth factor that is synthesized by various neural and neuroendocrine cells. The major pro-GRP hormone (isoform I) contains both GRP1-27 and a novel C-terminal extension peptide termed pro-GRP31-125. In order to define potentially active neuropeptides that could be generated from this novel protein domain, we analyzed the posttranslational processing of endogenous human pro-GRP1-125 in a small-cell lung cancer cell line. Because such studies are much easier in an overexpression system, we investigated at the same time the posttranslational processing of baculovirus-expressed human pro-GRP1-125 in an insect ovary cell line. In the small-cell lung cancer cell line, GRP1-27 was cleaved as expected from the endogenous prohormone at a pair of basic amino acids (29 and 30) and alpha-amidated at its C-terminal methionine; however, a number of novel peptides were generated by additional cleavages in the pro-GRP31-125 domain. In the insect ovary cell line, GRP1-27 was cleaved from the expressed prohormone by a different mechanism, as were a number of other peptides that appeared to be similar in size to those produced by the human neuroendocrine tumor cell line. These data show for the first time that an insect ovary cell line that is widely used to overexpress proteins can process a human neuropeptide precursor. They also reveal the existence of novel pro-GRP-derived peptides that are candidates for biologically active ligands.
How to insure that data acquired to verify treaty compliance are trustworthy (1988)

The author presents a solution to the problem of how to make it possible for two mutually distrusting (and presumed deceitful) parties, the host and the monitor, to both trust a data acquisition system that informs the monitor and perhaps third parties, whether the host has or has not violated the terms of a treaty. He starts by assuming that such a data acquisition system exists, and that the opportunities for deception lie only in the manipulation, i.e. forgery, modification, retransmission, etc. The author shows that it is possible to satisfy simultaneously the interests of all parties. The technical device on which this resolution depends is the concatenation of two or more private authentication channels to create a system in which each participant need only trust that part of the whole that he or she contributed. In the resulting scheme, no part of the data need to be kept secret from any participant at any time; no party nor collusion of fewer than all of the parties can utter an undetectable forgery; no unilateral action on the part of any party can lessen the confidence of others as to the authenticity of the data, and third parties, i.e. arbiters, can be logically persuaded of the authenticity of data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The effects of variations in the number and sequence of targeting signals on nuclear uptake. (1988)

To determine if the number of targeting signals affects the transport of proteins into the nucleus, Xenopus oocytes were injected with colloidal gold particles, ranging in diameter from 20 to 280 A, that were coated with BSA cross-linked with synthetic peptides containing the SV-40 large T-antigen nuclear transport signal. Three BSA conjugate preparations were used; they had an average of 5, 8, and 11 signals per molecule of carrier protein. In addition, large T-antigen, which contains one signal per monomer, was used as a coating agent. The cells were fixed at various times after injection and subsequently analyzed by electron microscopy. Gold particles coated with proteins containing the SV-40 signal entered the nucleus through central channels located within the nuclear pores. Analysis of the intracellular distribution and size of the tracers that entered the nucleus indicated that the number of signals per molecule affect both the relative uptake of particles and the functional size of the channels available for translocation. In control experiments, gold particles coated with BSA or BSA conjugated with inactive peptides similar to the SV-40 transport signal were virtually excluded from the nucleus. Gold particles coated with nucleoplasmin, an endogenous karyophilic protein that contains five targeting signals per molecule, was transported through the nuclear pores more effectively than any of the BSA-peptide conjugates. Based on a correlation between the peri-envelope density of gold particles and their relative uptake, it is suggested that the differences in the activity of the two targeting signals is related to their binding affinity for envelope receptors. It was also determined, by performing coinjection experiments, that individual pores are capable of recognizing and transporting proteins that contain different nuclear targeting signals.
Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. (1994)

The WHO MONICA Project, although designed to study longitudinal trends within populations, provides the opportunity for relating rates of validated CHD deaths to nonfatal myocardial infarction across populations. There are major differences between populations in nonfatal as well as fatal coronary event rates. They refute suggestions that high CHD mortality rates are associated with high case-fatality rates or a relative excess of sudden deaths. The high proportion of CHD deaths for which no diagnostic information is available is a cause for concern.
Isolation, Purification, and Characterization of Amadoriase Isoenzymes (Fructosyl Amine-oxygen Oxidoreductase EC 1.5.3) from Aspergillus sp. (1997)

Four "amadoriase" enzyme fractions, which oxidatively degrade glycated low molecular weight amines and amino acids under formation of hydrogen peroxide and glucosone, were isolated from an Aspergillus sp. soil strain selected on fructosyl adamantanamine as sole carbon source. The enzymes were purified to homogeneity using a combination of ion exchange, hydroxyapatite, gel filtration, and Mono Q column chromatography. Molecular masses of amadoriase enzymes Ia, Ib, and Ic were 51 kDa, and 49 kDa for amadoriase II. Apparent kinetic constants for Nepsilon-fructosyl Nalpha-t-butoxycarbonyl lysine and fructosyl adamantanamine were almost identical for enzymes Ia, Ib, and Ic, but corresponding values for enzyme II were significantly different. FAD was identified in all enzymes based on its typical absorption spectrum. N-terminal sequence was identical for enzymes Ia and Ib (Ala-Pro-Ser-Ile-Leu-Ser-Thr-Glu-Ser-Ser-Ile-Ile-Val-Ile-Gly-Ala-Gly- Thr-Trp-Gly-) and Ic except that the first 5 amino acids were truncated. The sequence of enzyme II was different (Ala-Val-Thr-Lys-Ser-Ser-Ser-Leu-Leu-Ile-Val-Gly-Ala-Gly-Thr-Trp-Gly- Thr-Ser-Thr-). All enzymes had the FAD cofactor-binding consensus sequence Gly-X-Gly-X-X-Gly within the N-terminal sequence. In summary, these data show the presence of two distinct amadoriase enzymes in the Aspergillus sp. soil strain selected on fructosyl adamantanamine and induced by fructosyl propylamine. In contrast to previous described enzymes, these novel amadoriase enzymes can deglycate both glycated amines and amino acids.
Polyvalent cations inhibit human neutrophil chemotaxis by interfering with the polymerization of actin. (1990)

The effect of a series of di- and trivalent cations on the locomotor response of human neutrophils to the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated. Migration was assessed by the leading front method. The cations inhibited FMLP-stimulated chemotaxis in the rank order: Ni2+ approximately Co2+ greater than Sr2+ greater than Zn2+ greater than Mn2+ approximately La3+ greater than Cd2+ approximately Ba2+ much greater than Mg2+. Benzamil, which blocks Na+/Ca2+ exchange, did not alter chemotaxis by itself but prevented the suppressive effects of each of the polyvalent cations on motility. The ion selectivity sequence and the lack of activity of benzamil are strikingly different than for O(-2) generation, thereby implying different modes of action in the two functional expressions. The F-actin content of the cells was monitored by the fluorescence of rhodamine-phalloidin. Each of the cations displayed comparable efficacy in blocking the polymerization of actin in FMLP-activated cells. Likewise, benzamil exhibited a protective effect, completely overcoming the inhibitory action of the polyvalent cations. The results indicate that these foreign ions gain access to the cell interior via a benzamil-sensitive pathway, namely Na+/Ca2+ exchange. Upon entry into the cytosol, they then interfere with the formation of filaments from actin monomers. These studies help to shed light on the interaction of divalent cations with cytoskeletal and contractile elements in cell motility.
A novel junction-free BE-SONOS NAND flash (2008)

We have successfully demonstrated a novel junction-free BE-SONOS NAND Flash. Junction-free devices greatly improve the short channel effect and thus promise scaling of NAND Flash below 20 nm node. Instead of S/D junctions a very small space (Lt 30 nm) is left between adjacent devices. Junction is formed only at the outer region of NAND array, while there is no junction inside the array. Fringe field from the gate inverts the Si under the narrow space allowing conduction without a diffusion junction. Successful n-channel, p-channel and TFT BE-SONOS NAND devices are demonstrated using this technique. Simulation results suggest that this novel junction-free technique is scalable beyond 20 nm node. Moreover, the junction-free devices are unaffected by the thermal budget in the 3D TFT devices. This new device can be implemented in the current NAND Flash process without introducing new masks.
Dairy consumption and risk of type 2 diabetes mellitus in men: a prospective study. (2005)

Dietary patterns characterized by higher dairy intake, especially low-fat dairy intake, may lower the risk of type 2 diabetes in men.
Capillary Vessel Network Integration by Inserting a Vascular Pedicle Enhances Bone Formation in Tissue-Engineered Bone Using Interconnected Porous Hydroxyapatite Ceramics (2004)

The aim of the present study was to investigate the possibility of integrating porous hydroxyapatite (HA) ceramics with a capillary vessel network via insertion of a vascular pedicle, and to determine whether this procedure enhances new bone formation in tissue engineering of bone. First, synthetic interconnected porous HA (IP-CHA) was implanted subcutaneously into rat groin with or without insertion of superficial inferior epigastric vessels. At 6 weeks, IP-CHA with vascular insertion contained thick fibrous connective tissue with a number of large blood vessels that seemed to derive from the inserted vascular bundle. Next, IP-CHA loaded with recombinant human bone morphogenetic protein 2 (BMP, 2 or 10 microg/block) was implanted with or without vascular insertion. At 3 weeks, IP-CHA/BMP (10 microg) composite with vascular insertion exhibited abundant new bone formation in the pores of the deep portion close to the inserted vessels. In contrast, IP-CHA/BMP (10 microg) without vascular insertion showed poor bone formation. Histomorphometric analysis demonstrated that vascular insertion significantly increased new bone formation. In IP-CHAs with a lower dose of BMP (2 microg), no bone formation was found, with or without vascular insertion. These results suggest that the present system of integrating a vascular network with IP-CHA is a useful technique for bone tissue engineering.