gebhart/patrepeval huggingface dataset:
Polyamide Nucleic Acid Targeted to the Primer Binding Site of the HIV-1 RNA Genome Blocks in Vitro HIV-1 Reverse Transcription (1998)

We report here that polyamide nucleic acid (PNA) as well as a polyamide nucleic acid-DNA chimera complementary to the primer binding site of the HIV-1 genome can completely block priming by tRNA3Lys and consequently the in vitro initiation of reverse transcription by HIV-1 RT. Conventional heating and cooling is not required for annealing PNA analogs to the complementary nucleotide sequence as effective blockage of reverse transcription results from their invasion in the duplex region of preprimed U5-PBS HIV-1 RNA template-primer and was seen even at ambient temperature. Further, the extension of the initiated nascent (-) strand DNA can also be blocked by inclusion of another PNA, targeted to upstream sequences in the U5 region of the viral RNA. Interestingly, a PNA chimera having only two DNA nucleotides annealed with the U5-PBS RNA is recognized as a bonafide primer by HIV-1 RT, as the 3'OH end of the chimeric molecule is extended by the enzyme in the presence of dNTPs. A significant observation was that RNA/PNA or RNA/(PNA-DNA) hybrids were entirely resistant to the RNase H activity of HIV-1 RT. Furthermore, PNA invasion into the RNA/DNA hybrid completely prevented the cleavage of the RNA strand, suggesting that the RNase H activity of HIV-1 RT which was required in reverse transcription may also be inhibited by the PNA oligomer. These observations suggest that oligomeric PNAs targeted to various critical regions of the viral genome are likely to have strong therapeutic potential for interrupting multiple steps involved in the replication of HIV-1 and warrant serious investigation especially in the area of an effective delivery system.
In-situ flame measurements of NO and CO using Mid-IR QC lasers (2002)

Room-temperature Quantum Cascade Lasers (QCL) allow high-sensitivity measurements of trace gas absorption in the 4.6 to 11 micron wavelength region. Important combustion-generated pollutants such as CO and NO exhibit strong fundamental absorption bands in this region and sub-ppm detection limits are projected. The paper will present initial results for both species obtained in a laboratory flat flame burner.
Constitutively activated neu oncoprotein tyrosine kinase interferes with growth factor‐induced signals for gene activation (1991)

The neu receptor oncoprotein tyrosine kinase, capable of transforming cultured fibroblasts and causing mammary carcinomas in transgenic mice, carries a point mutation in its transmembrane domain and shows a constitutive tyrosine kinase activity. We analyzed the neu tyrosine kinase and its substrates in transfected NIH 3T3 fibroblasts by phosphotyrosine immunoblotting. Tyrosine phosphorylated proteins were similar but not identical in epidermal growth factor (EGF)-stimulated cells expressing the human EGF receptor (EGFR) or a chimeric EGFR/neu receptor but differed from phosphotyrosyl proteins constitutively expressed in neu oncogene-transformed cells. The neu oncoprotein in the latter cells was phosphorylated in tyrosine in a ligand-independent manner and had a shortened half-life in comparison with the normal neu protein. Tumor promoter pretreatment inhibited ligand-induced receptor tyrosine phosphorylation and decreased tyrosine phosphorylated neu oncoprotein. Prolonged pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also prevented the induction of immediate early growth factor-regulated genes in response to neu activation. Expression of the neu oncogene but not the protooncogene in NIH 3T3 cells was associated with enhanced levels of the jun and fos oncoproteins and loss of serum growth factor induction of immediate early mRNA responses. The constitutively activated neu oncoprotein tyrosine kinase thus deregulates cellular genomic responses to growth factors.
On the Feasibility of 1T Ferroelectric FET Memory Array (2022)

To fully exploit the ferroelectric field effect transistor (FeFET) as compact embedded nonvolatile memory for various computing and storage applications, it is desirable to use a single FeFET (1T) as a unit cell and arrange the cells into an array. However, many write mechanisms for an 1T FeFET array reported in the literature are yet to be validated experimentally. In this work, we performed a comprehensive experimental characterization on the write operations in an 1T- NOR and 1T- AND array using n-channel bulk FeFETs. We discovered that: 1) the source/drain contact can only supply minority carriers (i.e., electrons) to the channel for polarization screening during the low- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> TH state programming; 2) the body contact can not only supply majority carriers (i.e., holes) for efficient high- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> TH state write, but also depletion charge for low- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> TH state programming, though with lower efficiency; and 3) during the low/high- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> TH programming, only the path that can supply negative/positive screening charges, respectively, need to respond, which necessitates the application of proper write biases on the corresponding terminal. Based on the understanding of these write mechanisms, we show the importance of localized body contact or column-wise body contact for the successful high- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> TH state programming. We also show that the previously proposed C- AND write scheme fails to program the FeFET to the low- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}$ </tex-math></inline-formula> TH state for our devices. Finally, we propose several write schemes for both 1T- AND and 1T- NOR arrays for various scenarios providing insights for choosing the appropriate write scheme, which will facilitate the adoption of 1T FeFET memory arrays for emerging applications.
Viral Gene Delivery to Skeletal Muscle: Insights on Maturation-Dependent Loss of Fiber Infectivity for Adenovirus and Herpes Simplex Type 1 Viral Vectors (1997)

The mechanisms causing age-dependent loss of muscle fiber infectivity observed in vivo for both adenoviral (Ad) and herpes simplex virus type 1 (HSV-1) gene delivery vectors remain poorly understood. Here we investigate the possible bases for this phenomenon using the novel application of enzymatically isolated, viable, single muscle fibers. We show that maturation-dependent loss of fiber infectivity is recapitulated in single fibers, and, thus, is not solely due to host immune response. Using localized irradiation of muscle in vivo, we show data suggesting that Ad infectivity of differentiated myofibers depends, at least in part, on myoblasts to mediate fiber transduction. On the other hand, infection of single fibers by HSV-1 is not affected by irradiation. Using confocal microscopy, we show that the basal lamina of myogenic cells efficiently infected by HSV-1 is structurally less organized than that of fibers resistant to infection by HSV-1. As well, we show that single myofibers isolated from adult, basal lamina-defective mice (merosin-deficient, dy/dy) are at least 10-fold more susceptible to infection by HSV-1 than are myofibers isolated from control mice. Together, these observations support the hypothesis that the basal lamina acts as a physical barrier to HSV-1 infection of mature muscle.
Decade-long remissions of leukemia sustained by the persistence of activated CD4 + CAR T-cells (2021)

The adoptive transfer of T lymphocytes reprogrammed to target tumor cells has demonstrated significant potential in various malignancies. However, little is known about the long-term potential and the clonal stability of the infused cells. Here, we studied the longest persisting CD19-redirected chimeric antigen receptor (CAR) T cells to date in two chronic lymphocytic leukemia (CLL) patients who achieved a complete remission in 2010. CAR T-cells were still detectable up to 10+ years post-infusion, with sustained remission in both patients. Surprisingly, a prominent, highly activated CD4 + population developed in both patients during the years post-infusion, dominating the CAR T-cell population at the late time points. This transition was reflected in the stabilization of the clonal make-up of CAR T-cells with a repertoire dominated by few clones. Single cell multi-omics profiling via Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) with TCR sequencing of CAR T-cells obtained 9.3 years post-infusion demonstrated that these long-persisting CD4 + CAR T-cells exhibited cytotoxic characteristics along with strong evidence of ongoing functional activation and proliferation. Our data provide novel insight into the CAR T-cell characteristics associated with long-term remission in leukemia.
Design and Synthesis of Novel α1a Adrenoceptor-Selective Antagonists. 1. Structure−Activity Relationship in Dihydropyrimidinones (1999)

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.
Avoided-crossing based modal cut-off analysis of 19-cell double-cladding photonic crystal fibers (2012)

The modal cut-off properties of Yb-doped Double-Cladding Photonic Crystal Fibers (DC-PCFs) with 19-cell core have been analyzed considering an innovative approach, where the avoided crossing between the guided modes and the highest-index cladding mode of the real fiber is taken as the cut-off condition. A finite element-based full-vector modal solver has been applied to calculate the modes of DC-PCFs with different normalized air-hole size and core refractive index. Simulations have shown the possibility to find generalized results for the modal cut-off wavelengths of 19-cell DC-PCFs.
The Inhibitory Effects of Omega‐Conotoxins on Ca Channels and Synapsesa (1989)

Omega conotoxins are peptides from snail venom. Two variants, omega CgTX and omega CmTX derived from two species of Conus, are the subjects of this report. Part I of this report reviews and discusses the ability of these toxins to inhibit Ca channels and synapses in different tissues from various species of animals. The potencies of these toxins vary depending on the target tissue, consonant with the notion that synaptic Ca channels have changed in the course of evolution. Part II introduces the notion that in contrast to inorganic Ca channel blockers, which act by reducing the amount of Ca2+ ions that can permeate an open channel, omega toxins act by reducing the availability of functional Ca channels. Thus, Ca channel-inhibition by omega toxins and that by inorganic blockers are expected to produce qualitatively different alterations in the distribution of intracellular Ca2+. Consistent with this expectation, the dose-response curves of inorganic blockers and omega CmTX differ. The dose-response curves of inorganic blockers are thought to reflect the cooperativity of Ca2+ ions in mediating transmitter release. In contrast, comparison of experimental and theoretical dose-response curves of omega CmTX leads us to propose the hypothesis that Ca channels normally do not act cooperatively to effect transmitter release.
Dielectric spectroscopy of the twist grain boundary phase and smectic‐like behaviour in the Isotropic Phase (2005)

Dielectric properties of a novel liquid crystal with direct transition from isotropic to twist grain boundary (TGB) phase were studied. Measurements were performed over a wide range of temperature in the isotropic phase, TGBA, TGBC and SmC* phases. The Arrhenius plot of the relaxation frequency of the molecular process around the short axis shows a variation in the activation energy in the isotropic phase. This is attributed to smectic‐like fluctuations in the isotropic phase. The dielectric relaxation strength in the TGBC phase has anomalous behaviour in the vicinity of TGBC–SmC* transition. The single cellective process observed in the TGBC phase splits into two processes in the SmC* phase.
Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule. (1989)

The class I and class II major histocompatibility complex (MHC) antigens are polymorphic cell-surface glycoproteins that present antigenic peptides to T lymphocytes in the generation of immune responses. While much is known about the recognition and processing of antigens, the nature of T-cell recognition sites on MHC molecules is poorly understood. Both structural and functional studies have suggested that the two major alpha-helical regions of the class I MHC molecule not only define the site for binding of antigenic peptide but also provide potential sites for interaction of the MHC molecule with the T-cell receptor. A peptide derived from one of these regions on the H-2Kb molecule, peptide Kb163-174, was previously shown to specifically inhibit the stimulation of an alloreactive T-cell hybridoma. To further investigate the role of this region in the recognition of H-2Kb, the effects of peptide Kb163-174 on allospecific T-cell lines and clones were studied. When peptide Kb163-174 was cocultured with either an H-2Kbm10 anti-H-2Kb cytotoxic T-lymphocyte (CTL) clone or a CTL line, this peptide inhibited lysis of H-2Kb targets. Pretreatment experiments showed that the blockade was due to interaction of the peptide with the effector T cells. Surprisingly, peptide Kb163-174 also inhibited lysis of H-2Kb targets by H-2Kbm1-, H-2Kbm3-, H-2Kbm6, and H-2Kbm8-anti-H-2Kb CTLs. These CTLs, which identify multiple antigenic sites on H-2Kb in the alpha 1 and alpha 2 domains, are not directed against amino acid residues 163-174 of H-2Kb. In addition, peptide Kb163-174 specifically blocked lysis of only H-2Kb and not H-2Ld targets by a single bulk CTL culture that was alloreactive on both H-2Kb and H-2Ld. These results indicate that peptide Kb163-174 interferes with T-cell receptor engagement of a contact site on the H-2Kb molecule. Thus, amino acid residues 163-174 define a site used by many alloreactive T cells to engage the H-2Kb molecule.
Neural interferometry: first non-contact measurements of action potential-induced nerve swelling (2004)

A novel heterodyne dual-beam interferometer is used to perform non-contact measurements of swelling displacements in a lobster nerve bundle during the action potential. Displacements are ~1-8 nm in amplitude and ~10 ms in duration.
Inhibition of TGF-β Enhances the In Vivo Antitumor Efficacy of EGF Receptor–Targeted Therapy (2012)

EGF receptor (EGFR)-targeted monoclonal antibodies (mAb), such as cetuximab, execute their antitumor effect in vivo via blockade of receptor-ligand interactions and engagement of Fcγ receptors on immune effector cells that trigger antibody-dependent cell-mediated cytotoxicity (ADCC). We show that tumors counteract the in vivo antitumor activity of anti-EGFR mAbs by increasing tumor cell-autonomous expression of TGF-β. We show that TGF-β suppresses the expression of key molecular effectors of immune cell-mediated cytotoxicity, including Apo2L/TRAIL, CD95L/FasL, granzyme B, and IFN-γ. In addition to exerting an extrinsic inhibition of the cytotoxic function of immune effectors, TGF-β-mediated activation of AKT provides an intrinsic EGFR-independent survival signal that protects tumor cells from immune cell-mediated apoptosis. Treatment of mice-bearing xenografts of human head and neck squamous cell carcinoma with cetuximab resulted in emergence of resistant tumor cells that expressed relatively higher levels of TGF-β compared with untreated tumor-bearing mice. Although treatment with cetuximab alone forced the natural selection of TGF-β-overexpressing tumor cells in nonregressing tumors, combinatorial treatment with cetuximab and a TGF-β-blocking antibody prevented the emergence of such resistant tumor cells and induced complete tumor regression. Therefore, elevated levels of TGF-β in the tumor microenvironment enable tumor cells to evade ADCC and resist the antitumor activity of cetuximab in vivo. Our results show that TGF-β is a key molecular determinant of the de novo and acquired resistance of cancers to EGFR-targeted mAbs, and provide a rationale for combinatorial targeting of TGF-β to improve anti-EGFR-specific antibody therapy of EGFR-expressing cancers.
Reduction of parameter sensitivity in an induction motor current regulator using integrated pilot sensors in the low-side switches (2004)

A closed-loop synchronous-frame current regulator for an induction machine drive has been developed that is capable of delivering high-quality performance characteristics using integrated pilot current sensors in the three low-side switches of a three-phase bridge inverter. However, the necessary current reconstruction exhibits sensitivity to errors in the machine parameters that has been documented during this investigation. This work presents a technique for introducing a gated integrator into the controller gain amplifier that compensates for parameter errors using feedback information from all three of the phase currents during the periodic intervals when it is available. A numerical singularity in the current reconstruction algorithm during light-load operation is overcome by introducing an alternative first-order current estimator that is activated over narrow angular spans of the fundamental component vector rotation. This paper also presents an in-situ technique to compensate gain differences between the three pilot devices in the inverter unit. The effectiveness of these improvements is verified using experimental results.
Supplementary Figure S4 from Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma (2023)

Supplementary Figure S4 from Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma
Fabrication of OLED Devices on Engineered Plastic Substrates (2000)

Protective ultrabarrier coatings for displays on flexible polymeric film substrates were deposited. The ultrabarrier coatings met a number of tight performance specifications including low gas permeation, high conductivity transparent electrodes, chemical resistance, thermal stability and scratch resistance must be met. Transmission of oxygen and water vapors by native polymeric materials was sufficiently high to prohibit their use in LCD and OLED applications. A multilayer film structure with alternate layers of organic polymer and metal oxide, demonstrated oxygen and moisture permeation rates below the measurement limit of commercial instrumentation (<0.005 O2 cc/m2/day, H2O g/m2/day). This highly transparent, multilayer ultra-barrier coating, with and without ITO overocats, was deposited by roll-to-roll compatible, vacuum deposition processes. The process for vacuum evaporation of organic monomers and in-situ polymerization, was used to deposit the organic layers. This process was also used to encapsulate OLED structures on plastic, glass, and silicon. Flexible OLED devices have been successfully fabricated using these ultrabarrier substrates. Lifetimes of greater than 10,000 hours were achieved for encapsulated OLED devices. Performance of the OLED devices on plastic substrates was similar to those on glass substrates.
Advancements in Iterative Methods for Rational Approximation in the Frequency Domain (2007)

Rational approximation of frequency-domain responses is commonly used in electromagnetic transients programs for frequency-dependent modeling of transmission lines and to some extent, network equivalents (FDNEs) and transformers. This paper analyses one of the techniques [vector fitting (VF)] within a general iterative least-squares scheme that also explains the relation with the polynomial-based Sanathanan-Koerner iteration. Two recent enhancements of the original VF formulation are described: orthonormal vector fitting (OVF) which uses orthonormal functions as basis functions instead of partial fractions, and relaxed vector fitting (RVF), which uses a relaxed least-squares normalization for the pole identification step. These approaches have been combined into a single approach: relaxed orthonormal vector fitting (ROVF). The application to FDNE identification shows that ROVF offers more robustness and better convergence than the original VF formulation. Alternative formulations using explicit weighting and total least squares are also explored.
Learning the Unlearnable (1991)

We present a local perceptron-learning rule that either converges to a solution, or establishes linear nonseparability. We prove that when no solution exists, the algorithm detects this in a finite time (number of learning steps). This time is polynomial in typical cases and exponential in the worst case, when the set of patterns is <i>nonstrictly</i> linearly separable. The algorithm is local and has no arbitrary parameters.
Stable organic photosensitive devices with exciton-blocking charge carrier filters utilizing high glass transition temperature materials (2023)

Disclosed herein are stable organic photosensitive devices including at least one exciton-blocking charge carrier filter. The filters comprise a mixture of at least one wide energy gap material having a sufficiently high glass transition temperature, e.g., higher than the temperature or temperature range at which the device typically operates, higher than a highest operating temperature of the device, higher than a threshold temperature value, etc. and at least one electron or hole conducting material. As described herein, the novel filters simultaneously block excitons and conduct the desired charge carrier (electrons or holes).