gebhart/patrepeval huggingface dataset:
Locked Nucleic Acid Based Beacons for Surface Interaction Studies and Biosensor Development (2009)

DNA sensors and microarrays permit fast, simple, and real-time detection of nucleic acids through the design and use of increasingly sensitive, selective, and robust molecular probes. Specifically, molecular beacons (MBs) have been employed for this purpose; however, their potential in the development of solid-surface-based biosensors has not been fully realized. This is mainly a consequence of the beacon's poor stability because of the hairpin structure once immobilized onto a solid surface, commonly resulting in a low signal enhancement. Here, we report the design of a new MB that overcomes some of the limitations of MBs for surface immobilization. Essentially, this new design adds locked nucleic acid bases (LNAs) to the beacon structure, resulting in a LNA molecular beacon (LMB) with robust stability after surface immobilization. To test the efficacy of LMBs against that of regular molecular beacons (RMBs), the properties of selectivity, sensitivity, thermal stability, hybridization kinetics, and robustness for the detection of target sequences were compared and evaluated. A 25-fold enhancement was achieved for the LMB on surface with detection limits reaching the low nanomolar range. In addition, the LMB-based biosensor was shown to possess better stability, reproducibility, selectivity, and robustness when compared to the RMB. Therefore, as an alternative to conventional DNA and as a prospective tool for use in both DNA microarrays and biosensors, these results demonstrate the potential of the locked nucleic acid bases for nucleic acid design for surface immobilization.
Involvement of the Toll-Like Receptor/Nitric Oxide Signaling Pathway in the Pathogenesis of Cervical Cancer Caused by High-Risk Human Papillomavirus Infection (2017)

Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected. Expressions of key TLR/NO pathway genes (TLR3/4/7/8, NF-<i>κ</i>B p65, and iNOS) in cervical epithelial cells were detected by quantitative reverse transcription PCR. Expressions of TLR4, NF-<i>κ</i>B p65, and iNOS in CaSki, HeLa, and C33a cells were determined by Western blot. NO concentration in cervical canal of CC group was significantly higher than in other groups (<i>P</i> < 0.05). Positive rates of iNOS in cervical tissues were 72.1%, 28.2%, and 3.1% in the CC group, HR-HPV group, and controls, respectively (<i>P</i> < 0.05). Levels of TLR3, TLR4, TLR7, TLR8, NF-<i>κ</i>B p65, and iNOS in cervical epithelial cells were higher in CC group than in other groups (<i>P</i> < 0.05). Both mRNA and protein levels of TLR4, NF-<i>κ</i>B p65, and iNOS were higher in HPV-positive HeLa and CaSki cells than in HPV-negative C33a cells (<i>P</i> < 0.05). Together, these results suggest that TLR/NO signaling pathway may be involved in pathogenesis of cervical cancer caused by HR-HPV.
Electrodeposited Cu‐Ni Textured Superlattices (1988)

Artificially layered materials of alternating 2–3 nm thick copper and nickel layers have been produced by electrodeposition on oriented single‐crystal copper substrates. X‐ray diffraction examination of thin layers chemically removed from the substrate showed that a coherent, relatively homogeneous coating, with a strong epitaxial relationship, had been produced. In particular, artificially layered Cu‐Ni alloys displaying a textured [110] orientation were obtained by electrodeposition. Noncoherent nucleation leads to the presence of various amounts of randomly oriented alloy grains on all substrates but, in particular, for the [100] orientation.
Algorithms for autonomous exploration and estimation in compliant environments (2012)

SUMMARY This paper investigates algorithms for enabling surgical slave robots to autonomously explore shape and stiffness of surgical fields. The paper addresses methods for estimating shape and impedance parameters of tissue and methods for autonomously exploring perceived impedance during tool interaction inside a tissue cleft. A hybrid force-motion controller and a cycloidal motion path are proposed to address shape exploration. An adaptive exploration algorithm for segmentation of surface features and a predictor-corrector algorithm for exploration of deep features are introduced based on discrete impedance estimates. These estimates are derived from localized excitation of tissue coupled with simultaneous force measurements. Shape estimation is validated in ex-vivo bovine tissue and attains surface estimation errors of less than 2.5 mm with force sensing resolutions achievable with current technologies in minimally invasive surgical robots. The effect of scan patterns on the accuracy of the shape estimate is demonstrated by comparing the shape estimate of a Cartesian raster scan with overlapping cycloid scan pattern. It is shown that the latter pattern filters the shape estimation bias due to frictional drag forces. Surface impedance exploration is validated to successfully segment compliant environments on flexible inorganic models. Simulations and experiments show that the adaptive search algorithm reduces overall time requirements relative to the complexity of the underlying structures. Finally, autonomous exploration of deep features is demonstrated in an inorganic model and ex-vivo bovine tissue. It is shown that estimates of least constraint based on singular value decomposition of locally estimated tissue stiffness can generate motion to accurately follow a tissue cleft with a predictor-corrector algorithm employing alternating steps of position and admittance control. We believe that these results demonstrate the potential of these algorithms for enabling “smart” surgical devices capable of autonomous execution of intraoperative surgical plans.
Spin-dependent tunneling conductance ofFe|MgO|Fesandwiches (2001)

We present first-principles based calculations of the tunneling conductance and magnetoconductance of epitaxial $\mathrm{Fe}(100)|\mathrm{MgO}(100)|\mathrm{Fe}(100)$ sandwiches. Our results indicate that tunneling is much more interesting and complicated than the simple barrier model used previously. We obtain the following general results: (1) Tunneling conductance depends strongly on the symmetry of the Bloch states in the electrodes and of the evanescent states in the barrier layer. (2) Bloch states of different symmetry decay at different rates within the barrier. The decay rate is determined by the complex energy bands of the same symmetry in the barrier. (3) There may be quantum interference between the decaying states in the barrier. This leads to an oscillatory dependence of the tunneling current on ${k}_{\ensuremath{\Vert}}$ and a damped oscillatory dependence on barrier thickness. (4) Interfacial resonance states can allow particular Bloch states to tunnel efficiently through the barrier. For $\mathrm{Fe}(100)|\mathrm{MgO}(100)|\mathrm{Fe}(100)$ our calculations indicate that quite different tunneling mechanisms dominate the conductance in the two spin channels. In the majority channel the conductance is primarily via Bloch electrons with small transverse momentum. One particular state with ${\ensuremath{\Delta}}_{1}$ symmetry is able to effectively couple from the Fe into the MgO. In the minority channel the conductance is primarily through interface resonance states especially for thinner layers. We predict a large magnetoresistance that increases with barrier thickness.
Hepatitis C Virus Nonstructural 5A Protein Induces Interleukin-8, Leading to Partial Inhibition of the Interferon-Induced Antiviral Response (2001)

Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). The HCV nonstructural 5A (NS5A) protein has been implicated in HCV antiviral resistance in many studies. NS5A antagonizes the IFN antiviral response in vitro, and one mechanism is via inhibition of a key IFN-induced enzyme, the double-stranded-RNA-activated protein kinase (PKR). In the present study we determined if NS5A uses other strategies to subvert the IFN system. Expression of full-length NS5A proteins from patients who exhibited a complete response (FL-NS5A-CR) or were nonresponsive (FL-NS5A-NR) to IFN therapy in HeLa cells had no effect on IFN induction of IFN-stimulated gene factor 3 (ISGF-3). Expression of mutant NS5A proteins lacking 110 (NS5A-DeltaN110), 222 (NS5A-DeltaN222), and 334 amino-terminal amino acids and mutants lacking 117 and 230 carboxy-terminal amino acids also had no effect on ISGF-3 induction by IFN. Expression of FL-NS5A-CR and FL-NS5A-NR did not affect IFN-induced STAT-1 tyrosine phosphorylation or upregulation of PKR and major histocompatibility complex class I antigens. However, NS5A expression in human cells induced interleukin 8 (IL-8) mRNA and protein, and this effect correlated with inhibition of the antiviral effects of IFN in an in vitro bioassay. NS5A induced transcription of a reporter gene driven by the IL-8 promoter, and the first 133 bp of the IL-8 promoter made up the minimal domain required for NS5A transactivation. NS5A-DeltaN110 and NS5A-DeltaN222 stimulated the IL-8 promoter to higher levels than did the full-length NS5A protein, and this correlated with increased nuclear localization of the proteins. Additional mutagenesis of the IL-8 promoter suggested that NF-kappaB and AP-1 were important in NS5A-DeltaN222 transactivation in the presence of tumor necrosis factor alpha and that NF-IL-6 was inhibitory to this process. This study suggests that NS5A inhibits the antiviral actions of IFN by at least two mechanisms and provides the first evidence for a biological effect of the transcriptional activity of the NS5A protein. During HCV infection, viral proteins may induce chemokines that contribute to HCV antiviral resistance and pathogenesis.
Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity (2012)

Hepatotoxicity is a serious problem during drug development and for the use of many established drugs. For example, acetaminophen overdose is currently the most frequent cause of acute liver failure in the United States and Great Britain. Evaluation of the mechanisms of drug-induced liver injury indicates that mitochondria are critical targets for drug toxicity, either directly or indirectly through the formation of reactive metabolites. The consequence of these modifications is generally a mitochondrial oxidant stress and peroxynitrite formation, which leads to structural alterations of proteins and mitochondrial DNA and, eventually, to the opening of mitochondrial membrane permeability transition (MPT) pores. MPT pore formation results in a collapse of mitochondrial membrane potential and cessation of adenosine triphosphate synthesis. In addition, the release of intermembrane proteins, such as apoptosis-inducing factor and endonuclease G, and their translocation to the nucleus, leads to nuclear DNA fragmentation. Together, these events trigger necrotic cell death. Alternatively, the release of cytochrome c and other proapoptotic factors from mitochondria can promote caspase activation and apoptotic cell death. Drug toxicity can also induce an inflammatory response with the formation of reactive oxygen species by Kupffer cells and neutrophils. If not properly detoxified, these extracellularly generated oxidants can diffuse into hepatocytes and trigger mitochondrial dysfunction and oxidant stress, which then induces MPT and necrotic cell death. This review addresses the formation of oxidants and the defense mechanisms available for cells and applies this knowledge to better understand mechanisms of drug hepatotoxicity, especially acetaminophen-induced liver injury.
Liver Cancer: Connections with Obesity, Fatty Liver, and Cirrhosis (2015)

The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The most worrisome aspects of these new risk factors are their large spread in the general population and their link with HCC arising in noncirrhotic livers. HCC may be the presenting feature of an asymptomatic nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. The HCC risk connected to metabolic factors has been underestimated so far, and a poorer surveillance has prevented an adequate treatment. Systemic and hepatic molecular mechanisms involved in obesity- and NAFLD-induced hepatocarcinogenesis as well as potential early markers of HCC are being extensively investigated. This review summarizes current evidence linking obesity, NAFLD and liver cancer, discusses its clinical impact and describes the main mechanisms underlying this complex relationship.
Expression of the c-mpl proto-oncogene in human hematologic malignancies (1993)

Similar to two other hematopoietic growth factor receptors, the c-fms (macrophage colony-stimulating factor receptor) and the c-kit genes, c-mpl has been discovered through the study of oncogenic retroviruses. Unlike c-fms and c-kit, which both belong to a subgroup of tyrosine kinase receptors, the c-mpl proto-oncogene encodes a new member of the cytokine receptor superfamily. We have studied the expression of c-mpl in a series of 105 patients with hematologic malignancies using Northern blot analysis. The levels of c-mpl transcripts in lymphoid malignancies and in chronic myeloproliferative disorders were not significantly different from those found in normal bone marrow cells, in which c-mpl was barely detectable. In contrast, c-mpl expression was increased in 26 of 51 patients with acute myeloblastic leukemia (AML) and in 5 of 16 patients with myelodysplastic syndromes. Amplification of the c-mpl gene was detected in genomic DNA of one M4 AML patient. There was no significant correlation between c-mpl expression and the French-American-British classification of AML. Patients with high c-mpl expression appeared to belong to a subgroup of AML with a low rate of complete remission and a poor prognosis, including secondary leukemia and AML with unfavorable cytogenetic abnormalities.
Certain phosphoramidate derivatives of dideoxy uridine (ddU) are active against HIV and successfully by‐pass thymidine kinase (1994)

As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of the inactive nucleoside analogue, dideoxy uridine (ddU) are inhibitors of HIV replication at microM levels. Moreover, we note that certain phosphoramidate derivatives retain their activity in thymidine kinase-deficient cells, which indicates that they do indeed act by intracellular release of the free nucleotide, and that they successfully by-pass the nucleoside kinase. The increased structural freedom in drug design which this allows may have implications for dealing with the emergence of resistance and may stimulate the discovery of improved therapeutic agents.
Effects on Proliferation and Differentiation of Multipotent Bone Marrow Stromal Cells Engineered to Express Growth Factors for Combined Cell and Gene Therapy (2011)

A key mechanism for mesenchymal stem cells/bone marrow stromal cells (MSCs) to promote tissue repair is by secretion of soluble growth factors (GFs). Therefore, clinical application could be optimized by a combination of cell and gene therapies, where MSCs are genetically modified to express higher levels of a specific factor. However, it remains unknown how this overexpression may alter the fate of the MSCs. Here, we show effects of overexpressing the growth factors, such as basic fibroblast growth factor (bFGF), platelet derived growth factor B (PDGF-BB), transforming growth factor β(1) (TGF-β(1) ), and vascular endothelial growth factor (VEGF), in human bone marrow-derived MSCs. Ectopic expression of bFGF or PDGF-B lead to highly proliferating MSCs and lead to a robust increase in osteogenesis. In contrast, adipogenesis was strongly inhibited in MSCs overexpressing PDGF-B and only mildly affected in MSCs overexpressing bFGF. Overexpression of TGF-β(1) blocked both osteogenic and adipogenic differentiation while inducing the formation of stress fibers and increasing the expression of the smooth muscle marker calponin-1 and the chondrogenic marker collagen type II. In contrast, MSCs overexpressing VEGF did not vary from control MSCs in any parameters, likely due to the lack of VEGF receptor expression on MSCs. MSCs engineered to overexpress VEGF strongly induced the migration of endothelial cells and enhanced blood flow restoration in a xenograft model of hind limb ischemia. These data support the rationale for genetically modifying MSCs to enhance their therapeutically relevant trophic signals, when safety and efficacy can be demonstrated, and when it can be shown that there are no unwanted effects on their proliferation and differentiation.
Toroidal coil models for transcutaneous magnetic simulation of nerves (2001)

A novel design of coils for transcutaneous magnetic stimulation of nerves is presented. These coils consist of a toroidal winding around a high-permeability material (Supermendur) core embedded in a conducting medium. Theoretical numerical calculations are used to analyze the effect of the design parameters of these coils, such as coil width, toroidal radius, conducting layer thickness and core transversal shape on the induced electric fields in terms of the electric field strength and distribution. Results indicate that stimulation of nerves with these coils has some of the advantages of both electrical and magnetic stimulation. These coils can produce localized and efficient stimulation of nerves with induced electric fields parallel and perpendicular to the skin similar to surface electrical stimulation. However, they retain some of the advantages of magnetic stimulation such as no risk of tissue damage due to electrochemical reactions at the electrode interface and less uncomfortable sensations or pain. The driving current is reduced by over three orders of magnitude compared to traditional magnetic stimulation, eliminating the problem of coil heating and allowing for long duration and high-frequency magnetic stimulation with inexpensive stimulators.
Statistical trust establishment in wireless sensor networks (2007)

We present a new distributed approach that establishes reputation-based trust among sensor nodes in order to identify malfunctioning and malicious sensor nodes and minimize their impact on applications. Our method adapts well to the special characteristics of wireless sensor networks, the most important being their resource limitations. Our methodology computes statistical trust and a confidence interval around the trust based on direct and indirect experiences of sensor node behavior. By considering the trust confidence interval, we are able to study the tradeoff between the tightness of the trust confidence interval with the resources used in collecting experiences. Furthermore, our approach allows dynamic scaling of redundancy levels based on the trust relationship between the nodes of a wireless sensor network. Using extensive simulations we demonstrate the benefits of our approach over an approach that uses static redundancy levels in terms of reduced energy consumption and longer life of the network. We also find that high confidence trust can be computed on each node with a relatively small memory overhead and used to determine the level of redundancy operations among nodes in the system.
Dependence of efficient adenoviral gene delivery in malignant glioma cells on the expression levels of the Coxsackievirus and adenovirus receptor (2000)

The results of this study indicate that CAR expression is a critical determinant of transduction efficiencies in adenovirus-based gene therapy for human malignant gliomas.
An Alternative Role for Foxp3 As an Effector T Cell Regulator Controlled through CD40 (2013)

The BDC2.5 T cell clone is highly diabetogenic, but the transgenic mouse generated from that clone is surprisingly slow in diabetes development. Although defining pathogenic effector T cells in autoimmunity has been inconsistent, CD4(+) cells expressing the CD40 receptor (Th40 cells) are highly diabetogenic in NOD mice, and NOD.BDC2.5.TCR.Tg mice possess large numbers of these cells. Given the importance of CD40 for pathogenic T cell development, BDC2.5.CD40(-/-) mice were created. Regulatory T cells, CD4(+)CD25(hi)Foxp3(+), develop normally, but pathogenic effector cells are severely reduced in number. Th40 cells from diabetic BDC2.5 mice rapidly induce diabetes in NOD.scid recipients, but Th40 cells from prediabetic mice transfer diabetes very slowly. Demonstrating an important paradigm shift, effector Th40 cells from prediabetic mice are Foxp3(+). As mice age, moving to type 1 diabetes development, Th40 cells lose Foxp3. When Th40 cells that are Foxp3(+) are transferred to NOD.scid recipients, disease is delayed. Th40 cells that are Foxp3(-) rapidly transfer disease. Th40 cells from BDC2.5.CD40(-/-) mice do not transfer disease nor do they lose Foxp3 expression. Mechanistically, Foxp3(+) cells produce IL-17 but do not produce IFN-γ, whereas Foxp3(-) Th40 cells produce IFN-γ and IL-2. This poses a new consideration for the function of Foxp3, as directly impacting effector T cell function.
Amphiphilic Network as Nanoreactor for Enzymes in Organic Solvents (2004)

Enzymes are powerful biocatalysts that work naturally in water but are also active in organic solvents. Here, we present a nanophase-separated amphiphilic network, where an enzyme is entrapped into its hydrophilic domains. A substrate that diffuses into the other, hydrophobic, phase of such a network can access the biocatalyst via the extremely large interface. Entrapped horseradish peroxidase and chloroperoxidase showed dramatically increased activity and operational stability compared to the native enzymes.
Optimization of filtering in soliton fiber lasers (1994)

Experiments with varying filter bandwidth in a soliton fiber laser are reported. Continuous tuning over 50 nm was obtained for pulses of <400 fs duration. It is demonstrated that the spectral sidebands due to periodic perturbations may be reduced to at least 17 db below the peak of the pulse spectrum without affecting pulse duration.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>