gebhart/patrepeval huggingface dataset:
Wired-Enzyme Core−Shell Au Nanoparticle Biosensor (2008)

We report a fully integrated core-shell nanoparticle system responsive to glucose. The system is comprised of self-assembled glucose oxidase and an osmium molecular wire on core-shell Au nanoparticles. Characterization of the functional nanoparticles by spectroscopy, quartz crystal microbalance and electrochemical techniques has shown that the catalytically active shell has a structure as designed and all components are active in the self-assembled multilayer shell. Furthermore, amperometric reagentless detection of glucose and contactless photonic biosensing by the Os(II) resonant Raman signal have been demonstrated. The enzymatic reduction of FAD by glucose and further reduction of the Raman silent Os(III) by FADH 2 yields a characteristic enzyme-substrate calibration curve in the millimolar range. Furthermore, coupling of electronic resonant Raman of the osmium complex with the SERS amplification by Au NPs plasmon resonance has been demonstrated which leads to an extra enhancement of the biosensor signal. We present a proof of concept extending the work done with planar surfaces to core-shell NPs as an advance in the design of glucose-responsive chemistry detected by SERS-like methods.
Design of Sequence‐Specific DNA‐Binding Ligands (1997)

Abstract Double‐stranded DNA can be viewed as a multifunctional, modular receptor that can be read sequence‐selectively in a digital way (base pair per base pair) by a complementary, similarly modular ligand. This principle has been exploited in several approaches to design sequence‐specific DNA‐binding ligands, such as triplex‐forming oligonucleotides, peptide nucleic acids and minor groove binding polyamides.
Radicicol suppresses transformation and restores tropomyosin-2 expression in both ras- and MEK-transformed cells without inhibiting the Raf/MEK/ERK signaling cascade. (2001)

The antibiotic radicicol suppresses transformation in a variety of transformed cells. The antineoplastic effects of the drug have been attributed to the degradation of Raf and the inactivation of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling cascade. Here we demonstrate that radicicol induces cell spreading, suppresses anchorage-independent cell growth, and increases the expression of the high-molecular weight tropomyosin isoform TM-2 in cells stably expressing a constitutively active form of MEK-1 as well as in ras-transformed cells. Furthermore, the reverting effects of the drug are achieved at concentrations below those required to deplete Raf from the cell or to inhibit the phosphorylation of ERK or its substrates Elk and pp90(RSK). In contrast, low concentrations of radicicol significantly inhibited activator protein (AP-1) and serum response factor (SRF)-mediated transcription. The lack of correlation between the effects of radicicol on cell phenotype and on the signaling activities of the Raf/MEK/ERK pathway indicate that Raf depletion or disruption of proximal signaling events in the mitogen-activated protein kinase pathway are not the predominant mechanisms by which the drug suppresses the transformed phenotype. Our observation that low concentrations of radicicol block transcriptional activities mediated by AP-1 and SRF suggests that interference with signaling upstream of these transcription factors may contribute to the reverting effects of the drug.
Different Effect of Hydrogelation on Antifouling and Circulation Properties of Dextran–Iron Oxide Nanoparticles (2012)

Premature recognition and clearance of nanoparticulate imaging and therapeutic agents by macrophages in the tissues can dramatically reduce both the nanoparticle half-life and delivery to the diseased tissue. Grafting nanoparticles with hydrogels prevents nanoparticulate recognition by liver and spleen macrophages and greatly prolongs circulation times in vivo. Understanding the mechanisms by which hydrogels achieve this "stealth" effect has implications for the design of long-circulating nanoparticles. Thus, the role of plasma protein absorption in the hydrogel effect is not yet understood. Short-circulating dextran-coated iron oxide nanoparticles could be converted into stealth hydrogel nanoparticles by cross-linking with 1-chloro-2,3-epoxypropane. We show that hydrogelation did not affect the size, shape and zeta potential, but completely prevented the recognition and clearance by liver macrophages in vivo. Hydrogelation decreased the number of hydroxyl groups on the nanoparticle surface and reduced the binding of the anti-dextran antibody. At the same time, hydrogelation did not reduce the absorption of cationic proteins on the nanoparticle surface. Specifically, there was no effect on the binding of kininogen, histidine-rich glycoprotein, and protamine sulfate to the anionic nanoparticle surface. In addition, hydrogelation did not prevent activation of plasma kallikrein on the metal oxide surface. These data suggest that (a) a stealth hydrogel coating does not mask charge interactions with iron oxide surface and (b) the total blockade of plasma protein absorption is not required for maintaining iron oxide nanoparticles' long-circulating stealth properties. These data illustrate a novel, clinically promising property of long-circulating stealth nanoparticles.
Trans-chromosomal methylation (2012)

The epigenome plays a vital role in helping to maintain and regulate cell functions in all organisms. Alleles with differing epigenetic marks in the same nucleus do not function in isolation but can interact in trans to modify the epigenetic state of one or both alleles. This is particularly evident when two divergent epigenomes come together in a hybrid resulting in thousands of alterations to the methylome. These changes mainly involve the methylation patterns at one allele being changed to resemble the methylation patterns of the other allele, in processes we have termed trans-chromosomal methylation (TCM) and trans-chromosomal demethylation (TCdM). These processes are primarily modulated by siRNAs and the RNA directed DNA methylation pathway. Drawing from other examples of trans-allelic interactions, we describe the process of TCM and TCdM and the effect such changes can have on genome activity. Trans-allelic epigenetic interactions may be a common occurrence in many biological systems.
Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR (2003)

A method for obtaining strongly polarized nuclear spins in solution has been developed. The method uses low temperature, high magnetic field, and dynamic nuclear polarization (DNP) to strongly polarize nuclear spins in the solid state. The solid sample is subsequently dissolved rapidly in a suitable solvent to create a solution of molecules with hyperpolarized nuclear spins. The polarization is performed in a DNP polarizer, consisting of a super-conducting magnet (3.35 T) and a liquid-helium cooled sample space. The sample is irradiated with microwaves at approximately 94 GHz. Subsequent to polarization, the sample is dissolved by an injection system inside the DNP magnet. The dissolution process effectively preserves the nuclear polarization. The resulting hyperpolarized liquid sample can be transferred to a high-resolution NMR spectrometer, where an enhanced NMR signal can be acquired, or it may be used as an agent for in vivo imaging or spectroscopy. In this article we describe the use of the method on aqueous solutions of [13C]urea. Polarizations of 37% for 13C and 7.8% for 15N, respectively, were obtained after the dissolution. These polarizations correspond to an enhancement of 44,400 for 13C and 23,500 for 15N, respectively, compared with thermal equilibrium at 9.4 T and room temperature. The method can be used generally for signal enhancement and reduction of measurement time in liquid-state NMR and opens up for a variety of in vitro and in vivo applications of DNP-enhanced NMR.
Subwavelength lithography: an impact of photomask errors on circuit performance (2002)

The impact of photo mask manufacturing errors in the photolithography process and subsequently on the final device and test circuit (ring oscillator) performance are investigated. A statistical Monte Carlo process generates a population of normally distributed simulated photo mask errors during the reticle manufacturing process. Further steps predict how these photo mask errors impact printed poly gate patterns under different lithography conditions. Sensitivity analysis performed with the Sequoia Device Designer software tool identified the metal oxide semiconductor field effect transistor (MOSFET) channel length (L<SUB>poly</SUB>) as the most sensitive MOSFET parameter and an estimate of the distribution of device performance for realistic photo mask errors is made.
Histone H2B as an antigen recognized by lung cancer–specific human monoclonal antibody HB4C5 (1991)

Histone H2B was demonstrated to be an immunoreactive material recognized by the human monoclonal antibody HB4C5, which had been already established to be specific for lung cancers. The inhibitory effect of histone H2B on the activity of HB4C5 antibody to immunostain the cytoplasmic antigen in lung adenocarcinoma tissue indicated that histone H2B at least had antigenic determinant comparable to the cytoplasmic antigen. A mouse anti-histone H2B monoclonal antibody could immunostain the cytoplasm of lung adenocarcinoma cells in sliced tissue sections in the same manner as the human monoclonal antibody HB4C5. Enzyme-linked immunosorbent assay of HB4C5 antibody on plastic immunoplates coated with histone H2B also showed specific reactivity of this antibody with histone H2B, and the reaction was effectively inhibited when extra histone H2B or mouse anti-histone H2B monoclonal antibody was added to the reaction mixture. These results consistently lead us to a conclusion that histone H2B possesses antigenicity to the human monoclonal antibody HB4C5.
Characterization ofMSH2 andMLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer (1997)

Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline heterozygous inactivating mutations of MSH2 and MLH1 have been identified previously in a substantial fraction of individuals who are predisposed genetically to colorectal carcinoma (CRC) and other tumors of the HNPCC spectrum. With the aim of determining the relevance of these two genes in the Italian population, we submitted to mutational analysis a set of 17 HNPCC families, all of which fulfilled the "Amsterdam criteria." A combination of different techniques, including reverse transcription-polymerase chain reaction (RT-PCR) of long fragments and single-strand conformation polymorphism (SSCP) on cDNA and genomic DNA, allowed the identification of ten molecular variants, seven of which are predicted to inactivate mismatch repair function. The mutated predisposing gene was MSH2 in two families and MLH1 in five other families. All of the mutations were characterized by DNA sequencing and appeared to involve different molecular mechanisms, such as short in-frame and out-of-frame deletions, splicing errors, and nonsense mutations. This study also demonstrates that, in the Italian population, a considerable fraction of HNPCC families (at least 41%) is linked to MSH2 and MLH1 mutations.
Cluster Tools With Chamber Revisiting—Modeling and Analysis Using Timed Petri Nets (2004)

Timed Petri nets are formal models of discrete concurrent systems. Since the durations of all activities are included in the model descriptions, many performance characteristics can be derived from such models. In the case of cluster tools, net models represent the flow of wafers through the chambers of the tool as well as consecutive actions performed by the robotic transporter. Steady-state performance of cluster tools with chamber revisiting is investigated in this paper. A systematic development of detailed tool schedules, based on a general behavioral description of the tool, is proposed and is used to derive the corresponding Petri net models. Symbolic performance characteristics of the modeled tools are obtained by using place invariants, without exhaustive reachability analysis. Simple examples presented in the paper can be easily extended in many ways.
Feasibility of Telementoring Between Baltimore (USA) and Rome (Italy): The First Five Cases (2000)

International telementoring is a feasible technique that can enhance surgeon education and decrease the likelihood of complications attributable to inexperience with new operative techniques.
Phosphorylated inositol compounds in β-cell stimulus-response coupling (2002)

Pancreatic beta-cell function is essential for the regulation of glucose homeostasis in humans, and its impairment leads to the development of type 2 diabetes. Inputs from glucose and cell surface receptors act together to initiate the beta-cell stimulus-response coupling that ultimately leads to the release of insulin. Phosphorylated inositol compounds have recently emerged as key players at all levels of the stimulus-secretion coupling process. In this current review, we seek to highlight recent advances in beta-cell phosphoinositide research by dividing our examination into two sections. The first involves the events that lead to insulin secretion. This includes both new roles for inositol polyphosphates, particularly inositol hexakisphosphate, and both conventional and 3-phosphorylated inositol lipids. In the second section, we deal with the more novel concept of the autocrine role of insulin. Here, released insulin initiates signal transduction cascades, principally through the activity of phosphatidylinositol 3-kinase. This new round of signal transduction has been established to activate key beta-cell genes, particularly the insulin gene itself. More controversially, this insulin feedback has also been suggested to either terminate or enhance insulin secretion events.
Characterization of a Calcium-Activated Chloride Channel as a Shared Target of Th2 Cytokine Pathways and Its Potential Involvement in Asthma (2001)

Interleukin (IL)-9 is a T helper (Th) 2 cytokine recently implicated as an essential factor in determining susceptibility to asthma. Transgenic mice overexpressing IL-9 exhibit many features that are characteristic of human asthma. To better understand the mechanism by which IL-9 mediates the various biologic activities in asthma, we performed suppressive subtraction hybridization with whole lung from IL-9 transgenic and control mice. Here we report the identification of mCLCA3, a calcium-activated chloride channel that was specifically induced in the lung epithelium of IL-9 transgenic mice. Expression of mCLCA3 could also be induced by intratracheal administration of IL-9 or other Th2 cytokines (IL-4, IL-13), but not by interferon-gamma. Moreover, expression of mCLCA3 was induced in the lung of antigen-exposed mice, and this induction could be suppressed by neutralizing IL-9 antibody treatment, indicating IL-9 is both necessary and sufficient to induce mCLCA3 in this experimental model of asthma. Finally, we demonstrate that hCLCA1 is the human counterpart to mCLCA3 and is also induced in vitro in human primary lung cells by Th2 cytokine treatment. Together, these data strongly implicate the involvement of mCLCA3 (in mice) and hCLCA1 (in humans) in the pathogenesis of Th2 cytokine-mediated asthmatic disorders.
Rare cell isolation and analysis in microfluidics (2014)

Rare cells are low-abundance cells in a much larger population of background cells. Conventional benchtop techniques have limited capabilities to isolate and analyze rare cells because of their generally low selectivity and significant sample loss. Recent rapid advances in microfluidics have been providing robust solutions to the challenges in the isolation and analysis of rare cells. In addition to the apparent performance enhancements resulting in higher efficiencies and sensitivity levels, microfluidics provides other advanced features such as simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. All of these advantages make microfluidics an excellent platform to deal with the transport, isolation, and analysis of rare cells. Various cellular biomarkers, including physical properties, dielectric properties, as well as immunoaffinities, have been explored for isolating rare cells. In this Focus article, we discuss the design considerations of representative microfluidic devices for rare cell isolation and analysis. Examples from recently published works are discussed to highlight the advantages and limitations of the different techniques. Various applications of these techniques are then introduced. Finally, a perspective on the development trends and promising research directions in this field are proposed.
Australian rural football club leaders as mental health advocates: an investigation of the impact of the Coach the Coach project (2010)

Rural football clubs appear to be appropriate social structures to promote rural mental health awareness. Club leaders, including many coaches, benefit from MHFA training, reporting increased skills and confidence. Benefit to club players from this approach was less obvious. However, the generally positive findings of this study suggest further research in this area is desirable.
Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome (2012)

NALP-1 inflammasome proteins are potential biomarkers to assess TBI severity, outcome, and the secondary injury mechanisms impeding recovery, serving as adjuncts to clinical predictors.
Comprehensive Messenger Ribonucleic Acid Profiling Reveals That Peroxisome Proliferator-Activated Receptor γ Activation Has Coordinate Effects on Gene Expression in Multiple Insulin-Sensitive Tissues (2001)

Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, including the glitazone class of drugs, are insulin sensitizers that reduce glucose and lipid levels in patients with type 2 diabetes mellitus. To more fully understand the molecular mechanisms underlying their therapeutic actions, we have characterized the effects of the potent, tyrosine-based PPAR gamma ligand GW1929 on serum glucose and lipid parameters and gene expression in Zucker diabetic fatty rats. In time-course studies, GW1929 treatment decreased circulating FFA levels before reducing glucose and triglyceride levels. We used a comprehensive and unbiased messenger RNA profiling technique to identify genes regulated either directly or indirectly by PPAR gamma in epididymal white adipose tissue, interscapular brown adipose tissue, liver, and soleus skeletal muscle. PPAR gamma activation stimulated the expression of a large number of genes involved in lipogenesis and fatty acid metabolism in both white adipose tissue and brown adipose tissue. In muscle, PPAR gamma agonist treatment decreased the expression of pyruvate dehydrogenase kinase 4, which represses oxidative glucose metabolism, and also decreased the expression of genes involved in fatty acid transport and oxidation. These changes suggest a molecular basis for PPAR gamma-mediated increases in glucose utilization in muscle. In liver, PPAR gamma activation coordinately decreased the expression of genes involved in gluconeogenesis. We conclude from these studies that the antidiabetic actions of PPAR gamma agonists are probably the consequence of 1) their effects on FFA levels, and 2), their coordinate effects on gene expression in multiple insulin-sensitive tissues.
DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission (1998)

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.
Secure Web Tunneling. (1998)

The boundary of an organization does not always coincide with its firewall. A member of an organization that is outside the firewall may wish to access internal Web services with the same ease and security that are common within the firewall. At the same time, the firewall should still be able to perform adequate access control, logging, and auditing. In this paper, we describe a new technique for secure Web tunneling, which permits the desired outside access to internal Web services. We argue that this technique is preferable to alternatives such as special firewall configurations, IP tunneling, and reverse proxies. We describe an implementation of Web tunneling that relies mostly on common, off-the-shelf components.
Fatigue-crack propagation in Nitinol, a shape-memory and superelastic endovascular stent material (1999)

Improving the design and performance of medical stents for implantation in the human body is of current interest. This paper describes a study of fatigue-crack propagation behavior in the superelastic alloy Nitinol. Specifically, the objective of this work was to study the effect of environment on cyclic crack-growth resistance in an approximately 50Ni-50Ti (atom %) alloy and to provide the necessary data for the safe life prediction of Nitinol endovascular stents. The material selected for this study was heat treated such that it was superelastic at human body temperature; this was confirmed with monotonic uniaxial tensile tests. Characterization of fatigue-crack growth rates was performed at 37 degrees C on disk-shaped compact-tension samples in environments of air, aerated deionized water, and aerated Hank's solution (a simulated body fluid). The effect of cyclic loading on the uniaxial constitutive behavior was investigated at a strain range of 6.4%, and results indicate that the magnitude of available superelastic strain ( approximately 5.0%) is maintained even after cyclic softening. However, despite the persistence of nucleating the stress-induced martensitic phase after cycling with a maximum strain slightly below the plastic yield point, Nitinol was found to have the lowest fatigue-crack growth resistance of the principal metallic alloys currently used for implant applications.
Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma (2010)

In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can be circumvented remain undetermined. We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas. Here we show that BIM epigenetic silencing by concurrent promoter hypermethylation and deacetylation occurs frequently in primary BL samples and BL-derived cell lines. Remarkably, patients with BL with hypermethylated BIM presented lower complete remission rate (24% vs 79%; P = .002) and shorter overall survival (P = .007) than those with BIM-expressing lymphomas, indicating that BIM transcriptional repression may mediate tumor chemoresistance. Accordingly, by combining in vitro and in vivo studies of human BL-xenografts grown in immunodeficient RAG2(-/-)γc(-/-) mice and of murine B220(+)IgM(+) B-cell lymphomas generated in Eμ-MYC and Eμ-MYC-BIM(+/-) transgenes, we demonstrate that lymphoma chemoresistance is dictated by BIM gene dosage and is reversible on BIM reactivation by genetic manipulation or after treatment with histone-deacetylase inhibitors. We suggest that the combination of histone-deacetylase inhibitors and high-dose chemotherapy may overcome chemoresistance, achieve durable remission, and improve survival of patients with BL.