gebhart/patrepeval huggingface dataset:
Genetic Programming by the Proteolytic Fragments of the Amyloid Precursor Protein: Somewhere Between Confusion and Clarity (2003)

Mice engineered to overexpress disease-causing mutant amyloid precursor proteins (APP) display plaque deposition, but lack the hyperphosphorylated tau and massive neuronal loss characteristic of Alzheimer's disease (AD). Global gene expression profiles of brain regions from AD patients show upregulation of proapoptotic and inflammatory genes and down-regulation of neurotrophic, MAPK, phosphatase, and synaptic genes, while a profile of mice overexpressing a mutant APP shows the opposite trends in apoptotic and neurotrophic genes. The proteolytic fragments of the amyloid precursor protein have distinct biological actions. Both the gamma-secretase cleaved COOH-terminal fragment (CTFgamma) and the alpha-secretase cleaved NH2-terminal of APP (sAPPalpha) can regulate gene expression. While Abeta and CTFgamma can lead to toxicity and cell death, sAPPalpha promotes neurite outgrowth, enhances memory, and protects against a variety of insults, including Abeta toxicity. In AD, Abeta levels increase while sAPPalpha levels decrease. These subtleties in the levels of APP cleavage products are not reproduced in mice overexpressing mutant APP. In fact, the gene expression changes driven by sAPPalpha, such as increases in transthyretin and insulin-like growth factor 2, may protect these mice from high levels of Abeta.
Temporal and spatial expression of an intestinal Na+/PO43− cotransporter correlates with epithelial transformation during thyroid hormone-dependent frog metamorphosis (1997)

The amphibian intestine has two morphologically distinct structures during development. Early embryogenesis generates a simple, tube-like intestine in the tadpole whereas after thyroid hormone (T3)-dependent metamorphosis a newly remodeled adult intestine is formed similar to that of higher vertebrates. This change requires a drastic transformation of the epithelial layer We have isolated a Na+/PO4 3- cotransporter gene that may contribute to this transformation. The deduced amino acid sequence of this gene shows a high degree of homology to the mammalian renal Na+/PO4 3- cotransporters, which have little or no expression in organs other than the kidney. The frog gene is highly expressed and regulated by T3 in the intestine with little expression and/or regulation by T3 in most other organs. Its mRNA is restricted to the differentiated epithelial cells both in tadpoles and postmetamorphic frogs. Interestingly, its expression is low in premetamorphic tadpoles, but up-regulated when metamorphosis is initiated by endogenous T3. As the larval epithelium undergoes programmed cell death (apoptosis), the mRNa level drops to a minimum. Subsequently, the gene is reactivated at the tip region of the newly formed adult intestinal folds and a crest-trough polarity of expression is established by the end of metamorphosis. This temporal regulation profile is also reproduced when premetamorphic tadpoles are treated with T3 to induce precocious intestinal remodeling. These results suggest a possible role of the Na+/PO 4 3- cotransporter during metamorphosis and demonstrate that the adult epithelial cell differentiation pattern is established in the direction of crest-to-trough of the intestinal fold, concurrent with the epithelial morphogenic process.
In Vivo Imaging of Thrombin Activity in Experimental Thrombi With Thrombin-Sensitive Near-Infrared Molecular Probe (2002)

Thrombin activity can be imaged in vivo by using a novel thrombin-activatable and thrombin-specific NIR molecular probe. The thrombin probe could enhance the understanding of the role of thrombin in thrombogenesis and other homeostatic and pathological conditions.
Role of a New Mammalian Gene Family in the Biosynthesis of Very Long Chain Fatty Acids and Sphingolipids (2000)

Whereas the physiological significance of microsomal fatty acid elongation is generally appreciated, its molecular nature is poorly understood. Here, we describe tissue-specific regulation of a novel mouse gene family encoding components implicated in the synthesis of very long chain fatty acids. The Ssc1 gene appears to be ubiquitously expressed, whereas Ssc2 and Cig30 show a restricted expression pattern. Their translation products are all integral membrane proteins with five putative transmembrane domains. By complementing the homologous yeast mutants, we found that Ssc1 could rescue normal sphingolipid synthesis in the sur4/elo3 mutant lacking the ability to synthesize cerotic acid (C(26:0)). Similarly, Cig30 reverted the phenotype of the fen1/elo2 mutant that has reduced levels of fatty acids in the C(20)-C(24) range. Further, we show that Ssc1 mRNA levels were markedly decreased in the brains of myelin-deficient mouse mutants known to have very low fatty acid chain elongation activity. Conversely, the dramatic induction of Cig30 expression during brown fat recruitment coincided with elevated elongation activity. Our results strongly implicate this new mammalian gene family in tissue-specific synthesis of very long chain fatty acids and sphingolipids.
Factors that govern the specificity of transglutaminase-catalysed modification of proteins and peptides (1992)

Correspondence| March 15 1992 Factors that govern the specificity of transglutaminase-catalysed modification of proteins and peptides P J Coussons; P J Coussons Search for other works by this author on: This Site PubMed Google Scholar N C Price; N C Price Search for other works by this author on: This Site PubMed Google Scholar S M Kelly; S M Kelly Search for other works by this author on: This Site PubMed Google Scholar B Smith; B Smith Search for other works by this author on: This Site PubMed Google Scholar L Sawyer L Sawyer Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1992) 282 (3): 929–930. https://doi.org/10.1042/bj2820929 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation P J Coussons, N C Price, S M Kelly, B Smith, L Sawyer; Factors that govern the specificity of transglutaminase-catalysed modification of proteins and peptides. Biochem J 15 March 1992; 282 (3): 929–930. doi: https://doi.org/10.1042/bj2820929 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1992 The Biochemical Society, London1992 Article PDF first page preview Close Modal You do not currently have access to this content.
Sweeping-window arc therapy: an implementation of rotational IMRT with automatic beam-weight calculation (2005)

Sweeping-window arc therapy (SWAT) is a variation of intensity-modulated radiation therapy (IMRT) with direct aperture optimization (DAO) that is initialized with a leaf sequence of sweeping windows that move back and forth periodically across the target as the gantry rotates. This initial sequence induces modulation in the dose and is assumed to be near enough to a minimum to allow successful optimization, done with simulated annealing, without requiring excessive leaf speeds. Optimal beam weights are calculated analytically, with easy extension to allow for variable beam weights. In this paper SWAT is tested on a phantom model and clinical prostate case. For the phantom, constant and variable beam weights are used. Although further work (in particular, improving the dose model) is required, the results show SWAT to be a feasible approach to generating deliverable dynamic arc treatments that are optimized.
Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2 (2015)

Altiratinib (DCC-2701) was designed based on the rationale of engineering a single therapeutic agent able to address multiple hallmarks of cancer (1). Specifically, altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment through balanced inhibition of MET, TIE2 (TEK), and VEGFR2 (KDR) kinases. This profile was achieved by optimizing binding into the switch control pocket of all three kinases, inducing type II inactive conformations. Altiratinib durably inhibits MET, both wild-type and mutated forms, in vitro and in vivo. Through its balanced inhibitory potency versus MET, TIE2, and VEGFR2, altiratinib provides an agent that inhibits three major evasive (re)vascularization and resistance pathways (HGF, ANG, and VEGF) and blocks tumor invasion and metastasis. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases.
Trapped Ion Quantum Computation with Transverse Phonon Modes (2006)

We propose a scheme to implement quantum gates on any pair of trapped ions immersed in a large linear crystal, using interaction mediated by the transverse phonon modes. Compared with the conventional approaches based on the longitudinal phonon modes, this scheme is much less sensitive to ion heating and thermal motion outside of the Lamb-Dicke limit thanks to the stronger confinement in the transverse direction. The cost for such a gain is only a moderate increase of the laser power to achieve the same gate speed. We also show how to realize arbitrary-speed quantum gates with transverse phonon modes based on simple shaping of the laser pulses.
Ultrapure Blue Thermally Activated Delayed Fluorescence Molecules: Efficient HOMO–LUMO Separation by the Multiple Resonance Effect (2016)

Ultrapure blue-fluorescent molecules based on thermally activated delayed fluorescence are developed. Organic light-emitting diode (OLED) devices employing the new emitters exhibit a deep blue emission at 467 nm with a full-width at half-maximum of 28 nm, CIE coordinates of (0.12, 0.13), and an internal quantum efficiency of ≈100%, which represent record-setting performance for blue OLED devices.
Human Papillomavirus in the Oral Cavity of Patients with and without Renal Transplantation (2006)

This study investigates human papillomavirus (HPV) infection in the oral cavities of 88 Australian renal transplant recipients and 88 immunocompetent controls. Oral cavities were examined for lesions and brushings collected for HPV analysis by consensus PCR. No warts were identified; HPV DNA was detected in 18% of transplant versus 1% control samples (P<0.001). Cutaneous HPVs predominated. One patient had HPV16 in samples taken four years apart without evidence of associated lesions or malignancy. Transplant recipients were more likely than controls to have current cutaneous warts (P<0.001), fewer sexual partners (P=0.001), and to have never consumed alcohol (P=0.01). Among the transplant group, the risk of an HPV-positive sample was higher among older patients (P=0.05), and those with past cutaneous warts (P=0.04). This study extends previous surveys by encompassing overt and asymptomatic infection, a broad spectrum of cutaneous and genital HPVs, and by providing new data on risk factors for oral HPV infection.
Printing nanomaterials in shrinking gels (2018)

Photopatterning of reactive sites in gels enables arbitrary patterning of nanoparticles
Interactions of the Low Density Lipoprotein Receptor Gene Family with Cytosolic Adaptor and Scaffold Proteins Suggest Diverse Biological Functions in Cellular Communication and Signal Transduction (2000)

The members of the low density lipoprotein (LDL) receptor gene family bind a broad spectrum of extracellular ligands. Traditionally, they had been regarded as mere cargo receptors that promote the endocytosis and lysosomal delivery of these ligands. However, recent genetic experiments in mice have revealed critical functions for two LDL receptor family members, the very low density lipoprotein receptor and the apoE receptor-2, in the transmission of extracellular signals and the activation of intracellular tyrosine kinases. This process regulates neuronal migration and is crucial for brain development. Signaling through these receptors requires the interaction of their cytoplasmic tails with the intracellular adaptor protein Disabled-1 (DAB1). Here, we identify an extended set of cytoplasmic proteins that might also participate in signal transmission by the LDL receptor gene family. Most of these novel proteins are adaptor or scaffold proteins that contain PID or PDZ domains and function in the regulation of mitogen-activated protein kinases, cell adhesion, vesicle trafficking, or neurotransmission. We show that binding of DAB1 interferes with receptor internalization suggesting a mechanism by which signaling through this class of receptors might be regulated. Taken together, these findings imply much broader physiological functions for the LDL receptor family than had previously been appreciated. They form the basis for the elucidation of the molecular pathways by which cells respond to the diversity of ligands that bind to these multifunctional receptors on the cell surface.
Immune Globulin to Prevent Nosocomial Infections (1992)

With the introduction of intravenous formulations, the use of immune globulins, once limited to IgG replacement in severe humoral immunodeficiencies, has been extended to include the prevention or treatment of a wide variety of infections and immunologic disorders.1 , 2 Though the role of immune globulin in the prevention of systemic and sinopulmonary bacterial infections in agammaglobulinemia is well established, its role in the management of more subtle humoral immunodeficiencies associated with B-cell neoplasms, bone marrow transplantation, and IgG-subclass deficiencies remains controversial.1 , 2 In premature babies, a physiologic hypogammaglobulinemia due to reduced transplacental transfer and endogenous synthesis of IgG provides a strong rationale . . .
High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer. (1986)

The optimal dose of progesterone compounds for the treatment of breast cancer is unknown, but there is evidence to suggest a dose-response curve. We are testing the tolerability and efficacy of megestrol acetate administered orally and continuously in doses three to ten times higher than the standard dose of 160 mg/d. We have so far treated 33 patients with metastatic breast cancer and positive or unknown tumor hormone receptor status. Thirty patients had had documented disease progression with previous hormonal therapy, and 22 had failed with previous chemotherapy. Twenty-five patients had objectively measurable metastases. In this heavily pretreated group, the objective response rate was 40%; in addition, 32% of patients had stabilization of disease. Interestingly, ten of 12 patients who had developed disease progression while on standard-dose megestrol acetate therapy had objective response or stabilization on the higher dose. Toxicity was acceptable and reversible and included mild elevations of blood pressure and weight gain. Our results indicate that high-dose megestrol acetate is well-tolerated and highly active in advanced refractory breast cancer, and suggest a dose-response curve for the drug in the treatment of breast cancer.
Nonviral and viral delivery of a human immunodeficiency virus protective gene into primary human T cells. (1994)

Because AIDS has been refractory to traditional pharmacologic interventions, alternative approaches have been developed. Although the introduction of specific antiviral genes into T leukemia cells can provide relative resistance to human immunodeficiency virus (HIV) replication, the testing of such genes against primary viral isolates in human CD4+ lymphocytes has been limited, and safety questions remain regarding gene delivery into cells from HIV-infected patients. In this report, we evaluate the efficacy of a transdominant mutant protein, Rev M10, against cloned and primary HIV isolates in human peripheral blood lymphocytes and describe different methods of gene transfer into peripheral blood lymphocytes from HIV-infected individuals. We show that gold microparticles can mediate stable Rev M10 gene transfer into these cells. Introduction of Rev M10 by these techniques conferred resistance to HIV infection in vitro to cloned and clinical isolates. Nonviral delivery of HIV protective genes will facilitate the development of gene therapy for AIDS and the analysis of viral and cellular gene expression in human T lymphocytes.
Presence of Tissue Factor Pathway Inhibitor in Human Atherosclerotic Plaques Is Associated With Reduced Tissue Factor Activity (1998)

Taken together, these data suggest that biologically active TFPI is present within human atherosclerotic plaque and is associated with attenuated TF activity.
Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide. (2007)

These results suggest that 64Cu-CB-TE2A-c(RGDyK) selectively binds alpha(v)beta3 on osteoclasts and may potentially be used to identify increased numbers of osteoclasts in osteolytic bone diseases such as osteolytic bone metastasis and inflammatory osteolysis.
Anti-CCL2: building a reservoir or opening the floodgates to metastasis? (2015)

Neutralisation of macrophage chemoattractant C-C chemokine ligand 2 (CCL2) has shown reduced metastasis and enhanced survival in numerous experimental models of tumorigenesis. However, important new findings reported in Nature by Momo Bentires-Alj's laboratory demonstrate that withdrawal of anti-CCL2 treatment accelerates lung metastasis and death in mice. The study highlights the need to consider longer term consequences of therapeutic intervention of metastatic disease, especially with regard to transient interference with the tumour microenvironment.
Identification of HLA-DP polymorphism with DP alpha and DP beta probes and monoclonal antibodies: correlation with primed lymphocyte typing. (1987)

Thirty-four lymphoblastoid cell lines that had been previously typed for HLA-DP antigens by primed lymphocyte typing (PLT) were tested by Southern blotting and by ELISA. Using two DP beta probes and a DP alpha probe with a series of enzymes, it is possible to identify restriction fragment length polymorphism (RFLP) patterns characteristic of DPw1, -2, -3, -4, and possibly -5. ELISA typing results, based on two polymorphic DP antibodies DP11.1 and ILR1, were compared with PLT-defined and RFLP-defined types. Thus, using a range of probes and enzymes it is possible to identify DP polymorphism. The value of monoclonal antibodies for such studies is demonstrated, and the molecular data can, in some cases, pinpoint the amino acids responsible for the specificity of the monoclonal antibodies.
Obesity, migraine, and chronic migraine (2007)

Migraine and obesity are associated in several ways. First, both are prevalent and disabling disorders influenced by genetic and environmental risk factors. Second, migraine with aura, as obesity, seems to be a risk factor for cardiovascular events. Finally, large population-based studies suggest that obesity is a risk factor for chronic migraine after adjusting for comorbidities. In this article, we discuss plausible mechanisms that may account for this association. Several of the inflammatory mediators that are increased in obese individuals are important in migraine pathophysiology, including interleukins and calcitonin gene-related peptide (CGRP). These mediators may increase the frequency, severity, and duration of migraine attacks per se, which in turn would cause central sensitization. Repeated central sensitization may be associated with permanent neuronal damage close to the periaqueductal gray area, with poor modulation to pain. Obesity is also a state of sympathetic activation, which may contribute to increase in headache frequency. Furthermore, the levels of adiponectin are decreased in obesity. At low but not normal levels, adiponectin is nociceptive. Shared biologic predisposition may also play a major role. Orexins modulate both pain and metabolism. Dysfunction in the orexins pathways seems to be a risk factor for both conditions. Finally, conditions that are comorbid to both states (e.g., depression, sleep apnea) may also make the relationship between both diseases more complex.
A Model for the Spectral Albedo of Snow. II: Snow Containing Atmospheric Aerosols (1980)

Small highly absorbing particles, present in concentrations of only 1 part per million by weight (ppmw) or less, can lower snow albedo in the visible by 5–15% from the high values (96–99%) predicted for pure snow in Part I. These particles have, however, no effect on snow albedo beyond 0.9 μm wavelength where ice itself becomes a strong absorber. Thus we have an attractive explanation for the discrepancy between theory and observation described in Part I, a discrepancy which seemingly cannot be resolved on the basis of near-field scattering and nonsphericity effects. Desert dust and carbon soot are the most likely contaminants. But careful measurements of spectral snow albedo in the Arctic and Antarctic paint to a "grey" absorber, one whose imaginary refractive index is nearly constant across the visible spectrum. Thus carbon soot, rather than the red iron oxide normally present in desert dust, is strongly indicated at these sites. Soot particles of radius 0.1 μm, in concentrations of only 0.3 ppmw, can explain the albedo measurements of Grenfell and Maykut on Arctic Ice Island T-3. This amount is consistent with some observations of soot in Arctic air masses. 1.5 ppmw of soot is required to explain the Antarctic observations of Kuhn and Siogas, which seemed an unrealistically large amount for the earth's most unpolluted continent until we learned that burning of camp heating fuel and aircraft exhaust indeed had contaminated the measurement site with soot. Midlatitude snowfields are likely to contain larger absolute amounts of soot and dust than their polar counterparts, but the snowfall is also much larger, so that the ppmw contamination does not differ drastically until melting begins. Nevertheless, the variations in absorbing particle concentration which will exist can help to explain the wide range of visible snow albedos reported in the literature. Longwave emissivity of snow is unaltered by its soot and dust content. Thus the depression of snow albedo in the visible is a systematic effect and always results in more energy being absorbed at a snow-covered surface than would be the case for pure snow. Thus man-made carbon soot aerosol may continue to exert a significant warming effect on the earth's climate even after it is removed from the atmosphere.
A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins (2001)

Purification steps for isolating therapeutic proteins from human plasma showed the removal of both PrP(Sc) and TSE infectivity. PrP(Sc) partitioning coincided with infectivity partitioning, which showed a close relationship between PrP(Sc) and TSE infectivity. By exploiting this association, the in vitro Western blot assay for PrP(Sc) was valuable for estimating the partitioning of TSE infectivity during plasma protein purification.