gebhart/patrepeval huggingface dataset:
Variability in the stability of DNA–peptide nucleic acid (PNA) single-base mismatched duplexes: Real-time hybridization during affinity electrophoresis in PNA-containing gels (1998)

The stability of all single-base mismatched pairs between a peptide nucleic acid 11-mer and its complementary DNA has been quantified in terms of their melting temperature and compared with the limited amount of data published to date. The strength of the interaction was determined by an automated affinity-electrophoretic approach permitting the visualization, in real time, of hybridization between a physically immobilized peptide nucleic acid and a complementary DNA migrating in an electric field. The dissociation constants are in the range of 10(-7) M (for mismatches) to 10(-10) M (for fully complementary DNA), which are in excellent agreement with solution studies. These and other thermodynamic constants can be accurately, rapidly, and reproducibly measured in this system at concentrations approaching dissociation conditions by using fluorescently labeled DNA in conjunction with commercial DNA sequencers. The stability of single-base mismatched peptide nucleic acid-DNA duplexes depends both on the position as well as on the chemical nature of the mismatch. The stability is at a minimum when the mutation is positioned 4 bases from either terminus (a loss of 20 degreesC or more in the melting temperature) but regains substantial stability when the mismatch is at the center of the duplex. The most stable mismatched pairs are G:T and T:T whereas destabilization is maximal for A:A and G:G. These observations are of significance in the design of probes for detecting mutations by hybridization.
Stereoscopic acuity with defocused and spatially filtered retinal images (1980)

Spectacle blur decreases stereoacuity more than ordinary visual acuity, and this cannot be accounted for by contrast reduction or by accommodation and/or convergence instability. Stereoscopic acuity was measured over a range of defocus exceeding 2 D in normal subjects with a 3-mm artificial pupil. Blur of one eye leads to a decrement in stereoacuity that is at least as high and usually higher than blur of both eyes; blurring only the disparate element of the pattern while keeping the rest clear is nearly as detrimental as blurring the whole pattern. In a separate experiment, the individual line elements of the pattern were subjected to spatial frequency filtering in the horizontal direction. For best stereoacuity values, representation of the whole spatial frequency spectrum is required. Patterns with diminished high-frequency content (&gt; 10 cycles/deg) show lowered stereoacuity and those utilizing predominantly a spatial frequency band centered on 22 cycles/deg even more so.
Aberrant Regulation of the BST2 (Tetherin) Promoter Enhances Cell Proliferation and Apoptosis Evasion in High Grade Breast Cancer Cells (2013)

Normal cellular phenotypes that serve an oncogenic function during tumorigenesis are potential candidates for cancer targeting drugs. Within a subset of invasive primary breast carcinoma, we observed relatively abundant expression of Tetherin, a cell surface protein encoded by the Bone Marrow Stromal Cell Antigen (BST2) known to play an inhibitory role in viral release from infected immune cells of the host. Using breast cancer cell lines derived from low and intermediate histopathologic grade invasive primary tumors that maintain growth-suppressive TGFβ signaling, we demonstrate that BST2 is negatively regulated by the TGFβ axis in epithelial cells. Binding of the transcription factor AP2 to the BST2 promoter was attenuated by inhibition of the TGFβ pathway thereby increasing BST2 expression in tumor cells. In contrast, inherent TGFβ resistance characteristic of high grade breast tumors is a key factor underlying compromised BST2 regulation, and consequently its constitutive overexpression relative to non-malignant breast epithelium, and to most low and intermediate grade cancer cells. In both 2-dimensional and 3-dimensional growth conditions, BST2-silenced tumor cells displayed an enhancement in tamoxifen or staurosporine-induced apoptotic cell death together with a reduction in the S-phase fraction compared to BST2 overexpressing counterparts. In a subset of breast cancer patients treated with pro apoptotic hormonal therapy, BST2 expression correlated with a trend for poor clinical outcome, further supporting its role in conferring an anti apoptotic phenotype. Similar to the effects of gene manipulation, declining levels of endogenous BST2 induced by the phytoalexin - resveratrol, restored apoptotic function, and curbed cell proliferation. We provide evidence for a direct approach that diminishes aberrant BST2 expression in cancer cells as an early targeting strategy to assist in surmounting resistance to pro apoptotic therapies.
Macrocyclic Pyridyl Polyoxazoles: Selective RNA and DNA G-Quadruplex Ligands as Antitumor Agents (2010)

The synthesis of a series of 24-membered pyridine-containing polyoxazole macrocycles is described. Seventeen new macrocycles were evaluated for cytotoxic activity against RPMI 8402, KB-3, and KB-3 cell lines that overexpress the efflux transporters MDR1 (KBV-1) and BCRP (KBH5.0). Macrocycles in which the pyridyl-polyoxazole moiety is linked by a 1,3-bis(aminomethyl)phenyl group with a 5-(2-aminoethyl)- (18) or a 5-(2-dimethylaminoethyl)- substituent (19) displayed the greatest cytotoxic potency. These compounds exhibit exquisite selectivity for stabilizing G-quadruplex DNA with no stabilization of duplex DNA or RNA. Compound 19 stabilizes quadruplex mRNA that encodes the cell-cycle checkpoint protein kinase Aurora A to a greater extent than the quadruplex DNA of a human telomeric sequence. These data may suggest a role for G-quadruplex ligands interacting with mRNA being associated with the biological activity of macrocyclic polyoxazoles. Compound 19 has significant in vivo anticancer activity against a human breast cancer xenograft (MDA-MB-435) in athymic nude mice.
Fluorochrome-labeled Tyramides: Use in Immunocytochemistry and Fluorescence In Situ Hybridization (1997)

The peroxidase-mediated deposition of hapten- and fluorochrome-labeled tyramides has recently been shown to increase the sensitivity of immunofluorescence and fluorescence in situ hybridization techniques. We have evaluated a number of red, green, and blue fluorescent tyramides for detection of antigens in tissue sections and cytospin preparations and for the detection of hapten- and horseradish peroxidase-labeled probes hybridized in situ to cells and chromosomes. With few exceptions, all fluorescent tyramide-based methods provided a considerable increase in sensitivity compared to conventional immunofluorescence and FISH methods.
Septicemia in U.S. Hospitals, 2009 (2011)

According to the obtained results of the current study, the content of referral letters were insufficient or inappropriate. Therefore, it is recommended to improve otolaryngology syllabus and provide suitable courses for undergraduate students in order to become familiar with the importance of referral letter writing.
Genetic Analysis (1998)

The genetic behavior of Arabidupsis is not different from that of other diploid organisms, and therefore one can find the topics of this chapter in almost any handbook of genetics. It is only owing to the specific (reproductive) biology of a species that sometimes a certain analytical procedure is favored over another one For Arabidopsis the fact that it is a self-fertilizing species and that it has relatively small flowers are important in this respect.
Magnetization process observation of a CoNiCr film in the field of a weakly excited objective lens in transmission electron microscope (1993)

Dynamic observation of the magnetization process of a fcc CoNiCr thin film has been made by tilting the specimen in the magnetic field of a weakly excited objective lens in a transmission electron microscope. Domain wall motion, magnetization direction rotation, and pinning effect due to surface NaCl contamination have been clearly revealed by this method for the film.
Gesturing in the Wild: Understanding the Effects and Implications of Gesture-Based Interaction for Dynamic Presentations (2010)

Driven by the increasing availability of low-cost sensing hardware, gesture-based input is quickly becoming a viable form of interaction for a variety of applications. Electronic presentations (e.g., PowerPoint, Keynote) have long been seen as a natural fit for this form of interaction. However, despite 20 years of prototyping such systems, little is known about how gesture-based input affects presentation dynamics, or how it can be best applied in this context. Instead, past work has focused almost exclusively on recognition algorithms. This paper explicitly addresses these gaps in the literature. Through observations of real-world practices, we first describe the types of gestures presenters naturally make and the purposes these gestures serve when presenting content. We then introduce Maestro, a gesture-based presentation system explicitly designed to support and enhance these existing practices. Finally, we describe the results of a real-world field study in which Maestro was evaluated in a classroom setting for several weeks. Our results indicate that gestures which enable direct interaction with slide content are the most natural fit for this input modality. In contrast, we found that using gestures to navigate slides (the most common implementation in all prior systems) has significant drawbacks. Our results also show how gesture-based input can noticeably alter presentation dynamics, often in ways that are not desirable.
The Prognostic Value of Tumor-Associated Macrophages in Leiomyosarcoma (2010)

Our data form an independent confirmation of the prognostic significance of TAMs and the CSF1 associated proteins in LMS. More aggressive or targeted therapies could be considered in the subset of LMS patients that highly express these markers.
Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double‐knockout mice (2013)

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by the lack of functional dystrophin. There is no cure, but several clinical trials aimed to restore the synthesis of functional dystrophin are underway. The dystrophin levels needed for improvement of muscle pathology, function, and overall vitality are not known. Here, we describe the mdx/utrn(-/-)/Xist(Δhs) mouse model, which expresses a range of low dystrophin levels, depending on the degree of skewing of X inactivation in a utrophin-negative background. Mdx/utrn(-/-) mice develop severe muscle weakness, kyphosis, respiratory and heart failure, and premature death closely resembling DMD pathology. We show that at dystrophin levels < 4%, survival and motor function in these animals are greatly improved. In mice expressing >4% dystrophin, histopathology is ameliorated, as well. These findings suggest that the dystrophin levels needed to benefit vitality and functioning of patients with DMD might be lower than those needed for full protection against muscle damage.
Solution Structure of Polymyxins B and E and Effect of Binding to Lipopolysaccharide: An NMR and Molecular Modeling Study (1999)

The cyclic decapeptides polymyxin B (PmB) and E (PmE) (mo-K'TK'-cyclo-[K'K'XLK'K'T]; mo, methyl octanoate; K', diaminobutyric acid; X, D-Phe (PmB) or D-Leu (PmE)) display antimicrobial and lipopolysaccharide (LPS) antagonistic activities. We have investigated the conformational behavior of PmB and PmE in water solution, free and bound to LPS, by homonuclear NMR and molecular modeling methods. The free peptides exist in equilibria of fast exchanging conformations with local preferences for a distorted type II' beta-turn from residues 5-8, and/or a gamma-turn in residue 10. These two motifs are not present in the bound conformation of the peptides. The latter is amphiphilic separating the two hydrophobic residues in the cycle from the positively charged diaminobutyric acid side chains by an envelope-like fold of the cycle. The bound conformation is used for the derivation of a model of the PmB-lipid A complex based on electrostatic interactions and reduction of hydrophobic area. The proposed mode of binding breaks up the supramolecular structure of LPS connected with its toxicity. The model should contribute to the understanding of entropy-driven PmB-lipid A binding at the molecular level and assist the design of inhibitors of endotoxic activity.
Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis. (1981)

Although it is generally accepted that negative venography excludes deep vein thrombosis (DVT) in patients in whom it is clinically suspected, there is no evidence to support this conclusion. To test the correctness of withholding anticoagulant therapy in these patients, we followed 160 consecutive patients who had clinically suspected DVT and negative venograms to determine the frequency of postvenographic DVT. Anticoagulant therapy was withheld in all patients. No patient died or developed pulmonary embolism during 3 months of follow-up. Two of the 160 patients (1.3%) attended the clinic on an emergency basis during follow-up with new symptoms of DVT and in both patients, DVT was confirmed by objective testing. These events developed within 5 days of venography, which suggests that they were induced by venography. Nevertheless, the findings indicate it is safe to withhold treatment in patients with clinically suspected DVT and negative venograms.
The Corticotropin-releasing Factor Receptor Type 2a Contains an N-terminal Pseudo Signal Peptide (2006)

The corticotropin-releasing factor receptor type 2a (CRF(2(a)) receptor) belongs to the family of G protein-coupled receptors. The receptor possesses a putative N-terminal signal peptide that is believed to be cleaved-off after mediating the endoplasmic reticulum targeting/insertion process, like the corresponding sequence of the homologous CRF(1) receptor. Here, we have assessed the functional significance of the putative signal peptide of the CRF(2(a)) receptor and show that it is surprisingly completely incapable of mediating endoplasmic reticulum targeting, despite meeting all sequence criteria for a functional signal by prediction algorithms. Moreover, it is uncleaved and forms part of the mature receptor protein. Replacement of residue Asn(13) by hydrophobic or positively charged residues converts the sequence into a fully functional and cleaved signal peptide demonstrating that conventional signal peptide functions are inhibited by a single amino acid residue. Deletion of the domain leads to an increase in the amount of immature, intracellularly retained receptors demonstrating that the sequence has adopted a new function in receptor trafficking through the early secretory pathway. Taken together, our results identify a novel hydrophobic receptor domain in the family of the heptahelical G protein-coupled receptors and the first pseudo signal peptide of a eukaryotic membrane protein. Our data also show that the extreme N termini of the individual CRF receptor subtypes differ substantially.
Anti-Tac(Fv)-PE40, a single chain antibody Pseudomonas fusion protein directed at interleukin 2 receptor bearing cells. (1990)

Anti-Tac(Fv)-PE40 is a chimeric single chain immunotoxin in which anti-Tac variable heavy and light chains held together by a peptide linker are attached to PE40, a truncated form of Pseudomonas exotoxin. This molecule was shown to be extremely cytotoxic for interleukin 2 (IL2) receptor bearing cells in tissue culture (Chaudhary, V. K., Queen, C., Junghans, R. P., Waldmann, T. A., FitzGerald, D. J., and Pastan, I. (1989) Nature 339, 394-397). Here we describe various forms of anti-Tac(Fv)-PE40 protein in which the order of the variable domains of anti-Tac has been switched and also three different types of peptide linkers have been used. All these proteins were purified to near homogeneity and were found to have similar cytotoxic activities against various human cells expressing the p55 subunit of the IL2 receptor. Anti-Tac(Fv)-PE40 was also found to have a very potent suppressive activity against phytohemagglutinin-activated human lymphoblasts and in a human mixed lymphocyte reaction. Anti-Tac(Fv)-PE40 appeared in the blood rapidly in mice after intraperitoneal administration and could be detected in the blood for up to 8 h. Anti-Tac(Fv)-PE40 warrants evaluation as an anti-tumor and immunosuppressive agent in humans.
Novel SiO/sub 2/AlN/HfAlO/IrO/sub 2/ memory with fast erase, large ΔV/sub TH/ and good retention (2005)

Using the strong trapping capability of novel AlN (k=10), low voltage drop in high-K layers and high workfunction IrO/sub 2/ with low leakage current, the SiO/sub 2//AlN/HfAlO(k=17)/IrO/sub 2/ device shows good 85/spl deg/C memory integrity of fast 100/spl mu/s erase, large 3.7V /spl Delta/V/sub th/ and 1.9V extrapolated memory window for 10-year retention at low 13V program/erase. These increase to 5.5V /spl Delta/V/sub th/ and 3.4V for 85/spl deg/C 10-year retention at 1ms erase.
Nonalcoholic Fatty Liver Disease: Pathogenesis and Potential for Nuclear Receptors as Therapeutic Targets (2007)

Nonalcoholic fatty liver disease (NAFLD) is a consequence of insulin resistance encompassing a spectrum that extends from simple hepatic steatosis through to nonalcoholic steatohepatitis (NASH), a condition that may progress to cirrhosis with its associated complications. A subset of nuclear receptors act as intracellular sensors for cholesterol metabolites, free fatty acids, and a range of other lipophilic molecules with pivotal roles in energy homeostasis and inflammation. These receptors represent attractive drug targets for the management of NAFLD and NASH as well as related conditions such as type 2 diabetes and the broader metabolic syndrome. To date, human studies have concentrated on peroxisome proliferator-activated receptor (PPAR) agonists, particularly those directed at PPARgamma. However, these drugs have significant limitations, so alternate approaches to nuclear receptor targeting are being explored.
Facile Synthesis of Hydroxy‐Functionalized Cycloolefin Copolymer Using ω‐Alkenylaluminium as a Comonomer (2013)

Copolymerization of norbornene and 7‐octenyldiisobutylaluminium is conducted by the catalytic system of ansa ‐dimethylsilylene(fluorenyl)(amido)dimethyltitanium, Me 2 Si(N t Bu)(fluorenyl)TiMe 2 ( 1 ), activated with Ph 3 CB(C 6 F 5 ) 4 to produce copolymers with pendant alkylaluminium groups. The termination of the copolymers with methanol gives poly(norbornene‐ co ‐oct‐1‐ene). Termination with oxygen gas gives poly(norbornene‐ co ‐oct‐1‐ene‐ co ‐oct‐7‐en‐1‐ol) because the oxidation of the pendant alkylaluminium groups with oxygen is not quantitative. Terpolymerization of norbornene, oct‐1‐ene, and 7‐octenyldiisobutylaluminium are also conducted, where the content of the hydroxy groups and the glass transition temperature are independently controlled by the molar ratio of each comonomer in feed. image
Protein Kinase C-α and ERK1/2 Mediate Mitochondrial Dysfunction, Decreases in Active Na+ Transport, and Cisplatin-induced Apoptosis in Renal Cells (2002)

Initiation of apoptosis by many agents is preceded by mitochondrial dysfunction and depolarization of the mitochondrial inner membrane. Here we demonstrate that, in renal proximal tubular cells (RPTC), cisplatin induces mitochondrial dysfunction associated with hyperpolarization of the mitochondrial membrane and that these events are mediated by protein kinase C (PKC)-alpha and ERK1/2. Cisplatin induced sustained decreases in RPTC respiration, oxidative phosphorylation, and increases in the mitochondrial transmembrane potential (deltaPsi(m)), which were preceded by the inhibition of F(0)F(1)-ATPase and cytochrome c release from the mitochondria, accompanied by caspase-3 activation, and followed by RPTC apoptosis. Cisplatin also decreased active Na+ transport as a result, in part, of the inhibition of Na+/K(+)-ATPase. These changes were preceded by PKC-alpha and ERK1/2 activation. Inhibition of cisplatin-induced PKC-alpha and ERK1/2 activation using Go6976 and PD98059, respectively, abolished increases in deltaPsi(m), diminished decreases in oxidative phosphorylation, active Na+ transport, and decreased caspase-3 activation without blocking cytochrome c release. Caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) did not prevent increases in deltaPsi(m). Furthermore, inhibition of PKC-alpha did not prevent cisplatin-induced ERK1/2 activation. We concluded that in RPTC: 1) cisplatin-induced mitochondrial dysfunction, decreases in active Na+ transport, and apoptosis are mediated by PKC-alpha and ERK1/2; 2) PKC-alpha and ERK1/2 mediate activation of caspase-3 by acting downstream of cytochrome c release from mitochondria; and 3) ERK1/2 activation by cisplatin occurs through a PKC-alpha-independent pathway.
Isolation of a primate embryonic stem cell line. (1995)

Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. Here we report the derivation of a cloned cell line (R278.5) from a rhesus monkey blastocyst that remains undifferentiated in continuous passage for > 1 year, maintains a normal XY karyotype, and expresses the cell surface markers (alkaline phosphatase, stage-specific embryonic antigen 3, stage-specific embryonic antigen 4, TRA-1-60, and TRA-1-81) that are characteristic of human embryonal carcinoma cells. R278.5 cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers but differentiate or die in the absence of fibroblasts, despite the presence of recombinant human leukemia inhibitory factor. R278.5 cells allowed to differentiate in vitro secrete bioactive chorionic gonadotropin into the medium, express chorionic gonadotropin alpha- and beta-subunit mRNAs, and express alpha-fetoprotein mRNA, indicating trophoblast and endoderm differentiation. When injected into severe combined immunodeficient mice, R278.5 cells consistently differentiate into derivatives of all three embryonic germ layers. These results define R278.5 cells as an embryonic stem cell line, to our knowledge, the first to be derived from any primate species.
Transmission of intense femtosecond laser pulses into dielectrics (2005)

The interaction of intense, femtosecond laser pulses with a dielectric medium is examined using a numerical simulation. The simulation uses the one-dimensional electromagnetic wave equation to model laser pulse propagation. In addition, it includes multiphoton ionization, electron attachment, Ohmic heating of free electrons, and temperature-dependent collisional ionization. Laser pulses considered in this study are characterized by peak intensities approximately 10(12) -10(14) W/cm(2) and pulse durations approximately 10-100 fsec . These laser pulses interacting with fused silica are shown to produce above-critical plasma densities and electron energy densities sufficient to attain experimentally measured damage thresholds. Significant transmission of laser energy is observed even in cases where the peak plasma density is above the critical density for reflection. A damage fluence based on absorbed laser energy is calculated for various pulse durations. The calculated damage fluence threshold is found to be consistent with recent experimental results.
Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum (2014)

Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations.