gebhart/patrepeval huggingface dataset:
The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases (2008)

Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.
Human natural killer cells and mature T lymphocytes express identical CD3ζ subunits as defined by cDNA cloning and sequence analysis (1990)

In order to characterize the CD3 zeta-related protein found in human natural killer (NK) cells and compare it with CD3 zeta expressed in T lymphocytes, the present study was performed. A polyclonal CD3-CD16+NK population displaying a strong non-major histocompatibility complex-restricted cytotoxic activity against the NK target K-562 was isolated and a product corresponding to CD3 zeta amplified using the polymerase chain reaction method. This 0.6-kb product was present in similar amounts in NK cells and T cells. In contrast, a product corresponding to CD3 delta was amplified from T lymphocytes exclusively. Thus, the CD3 zeta product detected in NK cells did not originate from contaminating T cells. DNA sequence analysis of two independent polymerase chain reaction products from the NK cells demonstrates that human NK cells and mature T cells share a CD3 zeta subunit with an identical primary amino acid sequence. The nucleotide sequence of a third NK-derived cDNA revealed an insertion of a CAG triplet encoding an additional glutamine residue in the cytoplasmic domain. Since this residue is encoded by nucleotides at a putative RNA splice junction, it possibly results from a difference in pre-mRNA splicing. Taken together, these data show that CD3 zeta is not structurally distinct in NK cells and in T lymphocytes.
Heterocyclic [4+ + 2] cycloadditions: the reactivity of pyridinium salts with electron-rich olefins (1990)

The N-(2,4-dinitrophenyl) salts of N,N-diethylnicotinamide and ethyl nicotinate undergo [4 + +2] cycloaddition with enol ethers at room temperature, providing the first examples of Bradsher cyclization by monocyclic quaternary aza-aromatics; other derivatives and salts of pyridine are inert under these conditions
Transport of protein hormones through the vascular endothelium (1995)

Introduction In most organs, the vascular endothelium forms a barrier through which the passage of macromolecules is slow and relatively inefficient (Williams 1983). Protein hormones are secreted at very low concentration and act rapidly at their target organs. There is thus a need for specific transendothelial transport mechanisms for these hormones. We will review here what is known about the structures of endothelial cells in relation to protein transport. We will then describe the specific mechanism we have recently observed for human chorionic gonadotropin/luteinizing hormone (hCG/LH) and discuss its potential generalization to the transendothelial transport of other hormones. The vascular endothelium constitutes a major barrier for the blood–tissue exchange of macromolecules The exchange of metabolites and secretory products between the blood and tissues takes place at the level of the microvasculature (i.e. in capillaries and venules). The vascular endothelium is the main barrier although the basal lamina, pericytes
Human Cord Blood CD34+CD38- Cell Transduction via Lentivirus-Based Gene Transfer Vectors (1999)

The efficient transfer and sustained expression of a transgene in human hematopoietic cells with in vivo repopulating potential would provide a significant advancement in the development of protocols for the treatment of hematopoietic diseases. Recent advances in the ability to purify and culture hematopoietic cells with the CD34+CD38- phenotype and with in vivo repopulating potential from human umbilical cord blood provide a direct means of testing the ability of transfer vectors to transduce these cells. Here we demonstrate the efficient transduction and expression of enhanced green fluorescent protein (EGFP) in human umbilical cord-derived CD34+CD38- cells, without prestimulation, using a lentivirus-based gene transfer system. Transduced CD34+CD38- cells cultured in serum-free medium supplemented with SCF, Flt-3, IL-3, and IL-6 maintained their surface phenotype for 5 days and expressed readily detectable levels of the transgene. The average transduction efficiency of the CD34+CD38- cells was 59 +/- 7% as determined by flow cytometry. Erythroid and myeloid colonies derived from transduced CD34+CD38- cells were EGFP positive at a high frequency (66 +/- 9%). In contrast, a murine leukemia virus-based vector transduced the CD34+CD38- cells at a low frequency (<4%). These results demonstrate the utility of lentiviral-based gene transfer vectors in the transduction of primitive human hematopoietic CD34+CD38- cells.
Genome mapping : a practical approach (1997)

1: Human linkage mapping. 2: Linkage mapping of plant and animal genomes. 3: Linkage mapping of quantitative trait loci in plants and animals. 4: Radiation hybrid mapping. 5: HAPPY mapping. 6: Construction and use of somatic cell hybrids. 7: The use of flow-sorted chromosomes in genome mapping. 8: The use of microdissected chromosomes in genome mapping. 9: Fluorescence in situ hybridization. 10: Contig assembly by fingerprinting. 11: Chromosome wallking. 12: Long-range restriction mapping of genomic DNA. Appendix 1 Core list of suppliers. Appendix 2 Non-commercial source for genome mapping. Appendix 3 Bioinformatics for genome mapping
Enabling Biological Nitrogen Fixation for Cereal Crops in Fertilized Fields (2021)

Agricultural productivity relies on synthetic nitrogen fertilizers, yet half of that reactive nitrogen is lost to the environment. There is an urgent need for alternative nitrogen solutions to reduce the water pollution, ozone depletion, atmospheric particulate formation, and global greenhouse gas emissions associated with synthetic nitrogen fertilizer use. One such solution is biological nitrogen fixation (BNF), a component of the complex natural nitrogen cycle. BNF application to commercial agriculture is currently limited by fertilizer use and plant type. This paper describes the identification, development, and deployment of the first microbial product optimized using synthetic biology tools to enable BNF for corn (<i>Zea mays</i>) in fertilized fields, demonstrating the successful, safe commercialization of root-associated diazotrophs and realizing the potential of BNF to replace and reduce synthetic nitrogen fertilizer use in production agriculture. Derived from a wild nitrogen-fixing microbe isolated from agricultural soils, <i>Klebsiella variicola</i> 137-1036 ("Kv137-1036") retains the capacity of the parent strain to colonize corn roots while increasing nitrogen fixation activity 122-fold in nitrogen-rich environments. This technical milestone was then commercialized in less than half of the time of a traditional biological product, with robust biosafety evaluations and product formulations contributing to consumer confidence and ease of use. Tested in multi-year, multi-site field trial experiments throughout the U.S. Corn Belt, fields grown with Kv137-1036 exhibited both higher yields (0.35 ± 0.092 t/ha ± SE or 5.2 ± 1.4 bushels/acre ± SE) and reduced within-field yield variance by 25% in 2018 and 8% in 2019 compared to fields fertilized with synthetic nitrogen fertilizers alone. These results demonstrate the capacity of a broad-acre BNF product to fix nitrogen for corn in field conditions with reliable agronomic benefits.
Vedolizumab for the Treatment of Ulcerative Colitis and Crohn‘s Disease (2012)

Crohn's disease and ulcerative colitis are chronic, relapsing inflammatory disorders of the GI tract. In both Crohn's disease and ulcerative colitis, leukocytic infiltration of the mucosa is associated with epithelial damage. Recently, monoclonal antibodies directed against cell adhesion molecules (CAMs) involved in leukocyte extravasation have been developed. Natalizumab, the first drug brought to market targeting CAMs, is clinically effective but is associated with serious adverse effects including the uncommon, but often fatal, neurological disease progressive multifocal leukoencephalopathy. Vedolizumab targets a subset of the CAMs blocked by natalizumab and is currently in Phase III trials to study its efficacy and safety in patients with inflammatory bowel disease. Here, we discuss the current treatment options available for patients with Crohn's disease or ulcerative colitis, the history of CAM inhibitors, the current state of development of vedolizumab and its future role in inflammatory bowel disease, if approved by regulatory agencies.
Electrodeposition of Ge, Si and SixGe1−x from an air- and water-stable ionic liquid (2008)

The electrodeposition of Ge, Si and, for the first time, of Si(x)Ge(1-x) from the air- and water-stable ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide ([Py(1,4)]Tf(2)N) containing GeCl(4) and/or SiCl(4) as precursors is investigated by cyclic voltammetry and high-resolution scanning electron microscopy. GeCl(2) in [Py(1,4)]Tf(2)N is electrochemically prepared in a two-compartment cell to be used as Ge precursor instead of GeCl(4) in order to avoid the chemical attack of Ge(iv) on deposited Ge. Silicon, germanium and Si(x)Ge(1-x) can be deposited reproducibly and easily in this ionic liquid. Interestingly, the Si(x)Ge(1-x) deposit showed a strong colour change (from red to blue) at room temperature during electrodeposition, which is likely to be due to a quantum size effect. The observed colours are indicative of band gaps between at least 1.5 and 3.2 eV. The potential of ionic liquids in Si(x)Ge(1-x) electrodeposition is demonstrated.
Studies on the Constituents of Asclepiadaceae Plants. XVI. On the Components of Metaplexis japonica MAKINO. III. The Structure of benzoylramanone. (1965)

The structure of benzoylramanone (III), a new ester type aglycone from Metaplexis japonica MAKINO, has been proved by chemical conversions and spectroscopic examination of the conversion products. The structural conclusion have been confirmed by correlation with a degradation product from hecogenin.
Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression (2000)

Although several CXC chemokines have been shown to induce angiogenesis and play roles in tumor growth, to date, no member of the CC chemokine family has been reported to play a direct role in angiogenesis. Here we report that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), induced chemotaxis of human endothelial cells at nanomolar concentrations. This chemotactic response was inhibited by a monoclonal antibody to MCP-1. MCP-1 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and the matrigel plug assays. As expected, the angiogenic response induced by MCP-1 was accompanied by an inflammatory response. With the use of a rat aortic sprouting assay in the absence of leukocytic infiltrates, we ruled out the possibility that the angiogenic effect of MCP-1 depended on leukocyte products. Moreover, the direct effect of MCP-1 on angiogenesis was consistent with the expression of CCR2, the receptor for MCP-1, on endothelial cells. Assessment of supernatant from a human breast carcinoma cell line demonstrated the production of MCP-1. Treatment of immunodeficient mice bearing human breast carcinoma cells with a neutralizing antibody to MCP-1 resulted in significant increases in survival and inhibition of the growth of lung micrometastases. Taken together, our data indicate that MCP-1 can act as a direct mediator of angiogenesis. As a chemokine that is abundantly produced by some tumors, it can also directly contribute to tumor progression. Therefore, therapy employing antagonists of MCP-1 in combination with other inhibitors of angiogenesis may achieve more comprehensive inhibition of tumor growth.
Strategies for Targeting Protein–Protein Interactions With Synthetic Agents (2005)

The development of small-molecule modulators of protein-protein interactions is a formidable goal, albeit one that possesses significant potential for the discovery of novel therapeutics. Despite the daunting challenges, a variety of examples exists for the inhibition of two large protein partners with low-molecular-weight ligands. This review discusses the strategies for targeting protein-protein interactions and the state of the art in the rational design of molecules that mimic the structures and functions of their natural targets.
Continuous-wave, short-wavelength infrared mixer using dispersion-stabilized highly-nonlinear fiber (2012)

A new type of highly nonlinear fiber (HNLF) was designed and fabricated. The new HNLF was engineered to reduce dispersion shift due to transverse fluctuations while maintaining the modal confinement superior to that of the conventional fibers. The new design strategy was validated by the measurements of the global and local dispersive characteristics under considerable core and index profile deformation induced by tensile stress, which indicated that the dispersive and phase matching characteristics of the fiber did not change even under the highest tensile stress. The characteristics effectively decoupled tension-based Brillouin suppression from phase-matching impairments in parametric mixers for the first time. The new HNLF was used to demonstrate the first coherence-preserving mixer operating in the short-wavelength infrared (SWIR) band. The SWIR mixer was driven by continuous-wave near-infrared (NIR) pump and did not require pump phase dithering to suppress Brillouin scattering.
A high-definition satellite television broadcast system—'MUSE' (1985)

The Japaneese Broadcasting Corporation&apos;s 1125-line HDTV system is described. Multiple sub-Nyquist sampling encoding is employed to achieve bandwidth compression of the time-division multiplexed signal used to convey luminance and colour information. Details are given of the system performance with particular reference to the effects of picture movement and resolution and noise.
Tunable Efficient Unitary Neural Networks (EUNN) and their application to RNNs (2016)

Using unitary (instead of general) matrices in artificial neural networks (ANNs) is a promising way to solve the gradient explosion/vanishing problem, as well as to enable ANNs to learn long-term correlations in the data. This approach appears particularly promising for Recurrent Neural Networks (RNNs). In this work, we present a new architecture for implementing an Efficient Unitary Neural Network (EUNNs); its main advantages can be summarized as follows. Firstly, the representation capacity of the unitary space in an EUNN is fully tunable, ranging from a subspace of SU(N) to the entire unitary space. Secondly, the computational complexity for training an EUNN is merely $\mathcal{O}(1)$ per parameter. Finally, we test the performance of EUNNs on the standard copying task, the pixel-permuted MNIST digit recognition benchmark as well as the Speech Prediction Test (TIMIT). We find that our architecture significantly outperforms both other state-of-the-art unitary RNNs and the LSTM architecture, in terms of the final performance and/or the wall-clock training speed. EUNNs are thus promising alternatives to RNNs and LSTMs for a wide variety of applications.
Epirubicin and Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Therapy for Early Breast Cancer (2006)

Epirubicin plus CMF is superior to CMF alone as adjuvant treatment for early breast cancer. (ClinicalTrials.gov number, NCT00003577 [ClinicalTrials.gov].).
DNA Damage-Induced Cell Cycle Regulation and Function of Novel Chk2 Phosphoresidues (2006)

Chk2 kinase is activated by DNA damage to regulate cell cycle arrest, DNA repair, and apoptosis. Phosphorylation of Chk2 in vivo by ataxia telangiectasia-mutated (ATM) on threonine 68 (T68) initiates a phosphorylation cascade that promotes the full activity of Chk2. We identified three serine residues (S19, S33, and S35) on Chk2 that became phosphorylated in vivo rapidly and exclusively in response to ionizing radiation (IR)-induced DNA double-strand breaks in an ATM- and Nbs1-dependent but ataxia telangiectasia- and Rad3-related-independent manner. Phosphorylation of these residues, restricted to the G(1) phase of the cell cycle, was induced by a higher dose of IR (>1 Gy) than that required for phosphorylation of T68 (0.25 Gy) and declined by 45 to 90 min, concomitant with a rise in Chk2 autophosphorylation. Compared to the wild-type form, Chk2 with alanine substitutions at S19, S33, and S35 (Chk2(S3A)) showed impaired dimerization, defective auto- and trans-phosphorylation activities, and reduced ability to promote degradation of Hdmx, a phosphorylation target of Chk2 and regulator of p53 activity. Besides, Chk2(S3A) failed to inhibit cell growth and, in response to IR, to arrest G(1)/S progression. These findings underscore the critical roles of S19, S33, and S35 and argue that these phosphoresidues may serve to fine-tune the ATM-dependent response of Chk2 to increasing amounts of DNA damage.
Detection of L‐nicotine with dissipation mode quartz crystal microbalance using molecular imprinted polymers (2012)

Abstract Synthetic materials with imprinted nanocavities can act as highly selective tailor‐made artificial receptors. Implementing these materials in a piezoelectric sensing device can offer fast and straightforward detection together with high sensitivity. L ‐nicotine, a major addictive substance in cigarettes is used as target molecule. The synthetic receptors for L ‐nicotine are made via the molecular imprinting technique. The target molecule is added to a monomer mixture containing initiator and this mixture is polymerized with heat. Subsequently, microparticles are obtained by crushing the bulk molecular imprinted polymers (MIPs), which are then immobilized on thin films of polyvinyl chloride. Using Quartz crystal microbalance, L ‐nicotine could be detected in the submicromolar range and the selectivity of the sensors was verified by reference measurements with L ‐cotinine. The effectiveness of the sensor was also tested for different aqueous fluids at different pH. It was found that MIPs bind 4.03 times more L ‐nicotine than non‐imprinted polymer in water and 1.99 times more in 0.1× phosphate buffer saline at pH 9.
19 F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons (2007)

MRI has been employed to elucidate the migratory behavior of stem/progenitor cells noninvasively in vivo with traditional proton (1H) imaging of iron oxide nanoparticle-labeled cells. Alternatively, we demonstrate that fluorine (19F) MRI of cells labeled with different types of liquid perfluorocarbon (PFC) nanoparticles produces unique and sensitive cell markers distinct from any tissue background signal. To define the utility for cell tracking, mononuclear cells harvested from human umbilical cord blood were grown under proendothelial conditions and labeled with nanoparticles composed of two distinct PFC cores (perfluorooctylbromide and perfluoro-15-crown-5 ether). The sensitivity for detecting and imaging labeled cells was defined on 11.7T (research) and 1.5T (clinical) scanners. Stem/progenitor cells (CD34+ CD133+ CD31+) readily internalized PFC nanoparticles without aid of adjunctive labeling techniques, and cells remained functional in vivo. PFC-labeled cells exhibited distinct 19F signals and were readily detected after both local and intravenous injection. PFC nanoparticles provide an unequivocal and unique signature for stem/progenitor cells, enable spatial cell localization with 19F MRI, and permit quantification and detection of multiple fluorine signatures via 19F MR spectroscopy. This method should facilitate longitudinal investigation of cellular events in vivo for multiple cell types simultaneously.
Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity (2016)

RORγt is the key transcription factor controlling the development and function of CD4<sup>+</sup> Th17 and CD8<sup>+</sup> Tc17 cells. Across a range of human tumors, about 15% of the CD4<sup>+</sup> T cell fraction in tumor-infiltrating lymphocytes are RORγ+ cells. To evaluate the role of RORγ in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate RORγ to a greater extent than the endogenous agonist desmosterol. These RORγ agonists enhance effector function of Type 17 cells by increasing the production of cytokines/chemokines such as IL-17A and GM-CSF, augmenting expression of co-stimulatory receptors like CD137, CD226, and improving survival and cytotoxic activity. RORγ agonists also attenuate immunosuppressive mechanisms by curtailing Treg formation, diminishing CD39 and CD73 expression, and decreasing levels of co-inhibitory receptors including PD-1 and TIGIT on tumor-reactive lymphocytes. The effects of RORγ agonists were not observed in RORγ-/- T cells, underscoring the selective on-target activity of the compounds. <i>In vitro</i> treatment of tumor-specific T cells with RORγ agonists, followed by adoptive transfer to tumor-bearing mice is highly effective at controlling tumor growth while improving T cell survival and maintaining enhanced IL-17A and reduced PD-1 <i>in vivo</i>. The <i>in vitro</i> effects of RORγ agonists translate into single agent, immune system-dependent, antitumor efficacy when compounds are administered orally in syngeneic tumor models. RORγ agonists integrate multiple antitumor mechanisms into a single therapeutic that both increases immune activation and decreases immune suppression resulting in robust inhibition of tumor growth. Thus, RORγ agonists represent a novel immunotherapy approach for cancer.
Apoptosis: lessons from in vitro systems (1995)

Although apoptosis is a major factor in metazoan morphogenesis and tissue homeostasis, its underlying biochemical mechanisms are poorly understood. This is now beginning to change as cell-free systems for the study of apoptosis start to reveal some of the activities involved. As suggested by earlier genetic analyses, a proteinase with properties resembling those of the interleukin-1-beta-converting enzyme (ICE) has been shown to initiate the apoptotic cascade in vitro. Curiously, results obtained with the cell-free systems suggest that essential downstream effectors of the apoptotic response may be intrinsic components of healthy nuclei.