gebhart/patrepeval huggingface dataset:
The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. (1992)

Homozygosity for the severe combined immunodeficiency (scid) mutation results in a block in T- and B-lymphocyte development. An unusually high incidence of spontaneous thymic lymphoma development was observed after transfer of this mutation from the C.B-17 congenic strain background onto the diabetes-susceptible nonobese diabetic (NOD) background. Thymomagenesis in the NOD-scid/scid mouse was associated with expression of an NOD mouse-unique endogenous ecotropic murine leukemia provirus locus (Emv-30, mapped to proximal region of chromosome 11) not expressed in the standard substrain NOD/Lt thymus. All tumors exhibited insertions of ecotropic proviruses, whereas only a subset also exhibited proviral integrations of mink cell focus-forming retrovirus. Neither class of retrovirus was associated with consistent integration into genes previously associated with activation of oncogenesis. We propose that the unusual features of T-cell ontogeny characteristic of the NOD inbred strain synergize with the scid-imparted block in thymocyte development, leading to activation of the NOD-unique Emv-30 to initiate thymomagenesis.
Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1. (1994)

Most proteoglycans bear either chondroitin sulfate or heparan sulfate chains linked to serine residues at Ser-Gly attachment sites on the core protein. However, only a fraction of proteins with Ser-Gly sites exhibit glycosaminoglycan chains. A variable proportion of these sites may be glycanated, and an unknown mechanism distinguishes whether these sites are for chondroitin sulfate or heparan sulfate. To evaluate the core protein features that determine whether and where chondroitin sulfate or heparan sulfate will be linked, we have studied mouse syndecan-1, a transmembrane proteoglycan that is invariably glycanated and can contain both chondroitin sulfate and heparan sulfate chains. The extracellular domain of the syndecan-1 core protein contains five Ser-Gly sites, three clustered near its N terminus and two adjacent to the transmembrane domain near its C terminus. We have established the distribution of glycosaminoglycans on these attachment clusters. In contrast to the C-terminal cluster, the N-terminal cluster was always glycanated, suggesting that this domain of the core protein contains sequences responsible for the invariable attachment of glycosaminoglycan chains. Solely chondroitin sulfate was found on the C-terminal cluster. This cluster contains the sequences EGSGE and ETSGE, both estimated to be on the protein surface in a hydrophilic environment. Heparan sulfate was found solely on the N-terminal cluster, which also bears some chondroitin sulfate. This cluster contains the sequences FSGSGTG and DGSGD, the former estimated to be in a hydrophobic pocket and the latter, similar to the sequence on the C-terminal cluster, in an exposed hydrophilic region. This glycosaminoglycan distribution was identical on mouse syndecan-1 produced by either mouse epithelial (NMuMG) or hamster mesenchymal (CHO) cells, suggesting that site-specific attachment of glycosaminoglycans is independent of cell type. These results implicate a cellular mechanism that distinguishes among the potential sites and attaches the correct glycosaminoglycan type unambiguously. Thus, structural elements of the core protein other than the Ser-Gly attachment sites determine if a site will be glycanated and, if so, whether with chondroitin sulfate or heparan sulfate.
Water desalination via capacitive deionization: what is it and what can we expect from it? (2015)

Capacitive deionization (CDI) is a promising technology for water desalination that has seen tremendous advances over the past five years.
Targeted In vivo Imaging of Integrin αvβ6 with an Improved Radiotracer and Its Relevance in a Pancreatic Tumor Model (2009)

The cell surface receptor alpha(v)beta(6) is epithelial specific, and its expression is tightly regulated; it is low or undetectable in adult tissues but has been shown to be increased in many different cancers, including pancreatic, cervical, lung, and colon cancers. Studies have described alpha(v)beta(6) as a prognostic biomarker linked to poor survival. We have recently shown the feasibility of imaging alpha(v)beta(6) in vivo by positron emission tomography (PET) using the peptide [(18)F]FBA-A20FMDV2. Here, we describe improved alpha(v)beta(6) imaging agents and test their efficacy in a mouse model with endogenous alpha(v)beta(6) expression. The modified compounds maintained high affinity for alpha(v)beta(6) and >1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved alpha(v)beta(6)-dependent binding in cell-based assays (>60% binding versus <10% for [(18)F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced alpha(v)beta(6) expression) or the BxPC-3 human pancreatic carcinoma cell line (endogenous alpha(v)beta(6) expression) revealed that the modified compounds showed significantly improved tumor retention. This, along with good clearance of nonspecifically bound activity, particularly for the new radiotracer [(18)F]FBA-PEG(28)-A20FMDV2, resulted in improved PET imaging. Tumor/pancreas and tumor/blood biodistribution ratios of >23:1 and >47:1, respectively, were achieved at 4 hours. Significantly, [(18)F]FBA-PEG(28)-A20FMDV2 was superior to 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) in imaging the BxPC-3 tumors. Pancreatic ductal adenocarcinoma is highly metastatic and current preoperative evaluation of resectability using noninvasive imaging has limited success, with most patients having metastases at time of surgery. The fact that these tumors express alpha(v)beta(6) suggests that this probe has significant potential for the in vivo detection of this malignancy, thus having important implications for patient care and therapy.
Intracellular Receptor Concentration Limits Glucocorticoid-Dependent Enhancer Activity* (1987)

The glucocorticoid receptor protein, in association with cognate hormonal ligands, binds with high affinity to specific DNA sequences termed glucocorticoid response elements (GREs) which can function as hormone-dependent transcriptional enhancers; thus, the receptor is a regulable enhancer-activating protein. We have constructed cell lines expressing different levels of glucocorticoid receptor, and demonstrate that the extent of a structural alteration in the chromatin at a characterized GRE, as well as the magnitude of several transcriptional responses elicited by the receptor, are roughly proportional to the number of receptor molecules per cell. Thus, for three independent glucocorticoid-responsive transcription units examined in our HTC-derived cell lines, the receptor appears to be a primary regulatory factor. Moreover, the results suggest that other cellular factors required for the assembly and function of GREs and transcription initiation complexes must be produced in excess relative to their levels of utilization at normal receptor concentrations.
Fourier Transform Raman Microscopic Mapping of the Molecular Components in a Human Tooth (1997)

Fourier transform Raman microscopic mapping was used to examine the distribution of the mineral and organic components in a cross-section of a human tooth. The relative distributions of carbonate and phosphate ions as well as the organic matrix components were plotted using functional group maps. The distribution of organic components was examined using the C–H stretch band between 2880 and 2700 cm-1. The distributions of phosphate and carbonate were determined using their respective symmetric stretching vibrations, νs(PO) at 961 cm-1 and νs(CO) at 1070 cm-1. Maps of the enamel–dentine junction at a high resolution of 10 μm showed that the amount of phosphate is lowest in this region. A series of spectra at 2 cm-1, ca. 20000 scans, used for curve fitting of the νs(CO) band was used to show that the concentration of carbonate ions in B-hydroxyapatite positions increases on going from the outside of the enamel towards the enamel–dentine junction. The results reveal that the deconvolution of the band envelope of νs(CO) and νas(PO), the antisymmetric stretching vibration of phosphate is more complicated than previously reported. The advantage of functional group Raman mapping is that, in addition to identifying the chemical constituents, valuable microstructural information is obtained including species distribution across the surface, and in particular at the enamel–dentine interface. Minimal, non-chemical sampling preparation means that spectral information obtained can be directly related to the physical properties and biological function of such tissues. © 1997 by John Wiley & Sons, Ltd.
Cubic Octanuclear Ni(II) Clusters in Highly Porous Polypyrazolyl-Based Materials (2010)

Two highly porous coordination polymers, containing rare octanuclear hydroxo-nickel clusters and long bis-pyrazolyl spacers, are shown to possess, after mild thermal treatment, lattice cavities up to 72% of the total crystal volume.
Tyrosine kinase inhibitors impair B-cell immune responses in CML through off-target inhibition of kinases important for cell signaling (2013)

Tyrosine kinase inhibitors (TKIs) have significant off-target multikinase inhibitory effects. We aimed to study the impact of TKIs on the in vivo B-cell response to vaccination. Cellular and humoral responses to influenza and pneumococcal vaccines were evaluated in 51 chronic phase chronic myeloid leukemia (CML) patients on imatinib, or second-line dasatinib and nilotinib, and 24 controls. Following vaccination, CML patients on TKI had significant impairment of IgM humoral response to pneumococcus compared with controls (IgM titer 79.0 vs 200 U/mL, P = .0006), associated with significantly lower frequencies of peripheral blood IgM memory B cells. To elucidate whether CML itself or treatment with TKI was responsible for the impaired humoral response, we assessed memory B-cell subsets in paired samples collected before and after imatinib therapy. Treatment with imatinib was associated with significant reductions in IgM memory B cells. In vitro coincubation of B cells with plasma from CML patients on TKI or with imatinib, dasatinib, or nilotinib induced significant and dose-dependent inhibition of Bruton's tyrosine kinase and indirectly its downstream substrate, phospholipase-C-γ2, both important in B-cell signaling and survival. These data indicate that TKIs, through off-target inhibition of kinases important in B-cell signaling, reduce memory B-cell frequencies and induce significant impairment of B-cell responses in CML.
HER-2/neu Gene Copy Number Quantified by Real-Time PCR: Comparison of Gene Amplification, Heterozygosity, and Immunohistochemical Status in Breast Cancer Tissue (2003)

The assay is suitable for accurate and precise quantification of HER-2/neu copy numbers in tumor tissue samples obtained in routine clinical practice.
Binding of APC to the Human Homolog of the Drosophila Discs Large Tumor Suppressor Protein (1996)

The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors, and its product binds to the adherens junction protein beta-catenin. Overexpression of APC blocks cell cycle progression. The APC-beta-catenin complex was shown to bind to DLG, the human homolog of the Drosophila discs large tumor suppressor protein. This interaction required the carboxyl-terminal region of APC and the DLG homology repeat region of DLG. APC colocalized with DLG at the lateral cytoplasm in rat colon epithelial cells and at the synapse in cultured hippocampal neurons. These results suggest that the APC-DLG complex may participate in regulation of both cell cycle progression and neuronal function.
Overview of Elizabeth’s Life and Reign (2002)

In early September 1533 Henry VIII was not the only one to eagerly anticipate the birth of his child by his second wife, Anne Boleyn, nor the only one to hope that this child would be a son. Everyone in England, and, indeed, Western Europe, was waiting. Henry would eventually have a son, Edward, but his short, unhappy reign would be eclipsed by the long and far more successful reign of his sister, Elizabeth. Her success demonstrated that Henry's belief that he must have a son to secure England's safety was misplaced. Nonetheless, Henry's desire for a male heir was understandable; we may, however, question if his anxiety justified his six marriages and the beheading of two of his wives.
L2DTL/CDT2 and PCNA Interact with p53 and Regulate p53 Polyubiquitination and Protein Stability through MDM2 and CUL4A/DDB1 Complexes (2006)

The CUL4-ROC1 E3 ligase complex regulates genome stability, replication and cell cycle progression. A novel WD40 domain-containing protein, L2DTL/CDT2 and PCNA were identified as proteins associated with CUL4/DDB1 complexes. Inactivation of CUL4A, L2DTL, PCNA, DDB1 or ROC1 induced p53 stabilization and growth arrest. L2DTL, PCNA and DDB1/CUL4A complexes were found to physically interact with p53 tumor suppressor and its regulator MDM2/HDM2. The isolated CUL4A complexes display potent and robust polyubiquitination activity towards p53 and this activity is dependent on L2DTL, PCNA, DDB1, ROC1 and MDM2/HDM2. We also found that the interaction between p53 and CUL4 complex is regulated by DNA damage. Our data further showed that MDM2/HDM2 is rapidly proteolyzed in response to UV irradiation and this process is regulated by CUL4/DDB1 and PCNA. Our studies demonstrate that PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells.
Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 4. Structure−Activity Relationship of Substituents on the Benzene Ring of the Cinnamide (2001)

We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activity over mono substitution on the ring. The best 2,3-substituents were chlorine and trifluoromethyl groups. Compounds 39 and 40 which contain two CF3 groups have IC(50) values of 0.5 and 0.1 nM, respectively, in inhibiting JY8 cells expressing LFA-1 on their surface, from adhering to ICAM-1. The structure-activity relationship (SAR) was examined using an NMR based model of the LFA-1 I domain/compound 31 complex. One of our compounds (38) was able to reduce cell migration in two different in vivo experiments.
Monitoring the cytosolic entry of cell-penetrating peptides using a pH-sensitive fluorophore (2014)

We report a simple, effective method to assess the cytosolic delivery efficiency and kinetics of cell-penetrating peptides using a pH-sensitive fluorescent probe, naphthofluorescein.
The effect of botulinum toxin A on gastrocnemius length: magnitude and duration of response (1999)

Thirty-nine ambulant children (22 with hemiplegia, 17 with diplegia) with spastic cerebral palsy receiving isolated gastrocnemius muscle injection with botulinum toxin A were studied prospectively. The children had a mean age of 6 years (range 3 to 13 years). Measurement of gastrocnemius muscle length was used to estimate the dynamic component of each child's spasticity and to quantify the response. There was a strong correlation between the dynamic component of spasticity before injection and the corresponding magnitude of the response after injection. Children undergoing repeated injections showed similar correlations. A strong correlation was found between the duration of response and the dynamic component. Children with hemiplegia showed twice the duration for a given dynamic component compared with those with diplegia when injected with the same total dose per unit body weight. Long-term lengthening did not occur for the cohort, although some patients showed a response at a 12-month follow-up. By delaying shortening, the injections may have a role in delaying the need for surgery. Injections were well tolerated with few side effects.
Surface Functionalization of Silica Nanoparticles with Cysteine: A Low-Fouling Zwitterionic Surface (2011)

Herein, we report on the functionalization of silica nanoparticles with a small molecule, the amino acid cysteine, in order to create a low-fouling zwitterionic surface for nanomedicine applications. The cysteine functionalization was shown to impart the particles with excellent stability in both salt and single-protein solutions of lysozyme (positively charged) and bovine serum albumin (negatively charged). Bare silica particles precipitated immediately in a lysozyme solution, while cysteine-functionalized particles were stable for 20 h. Furthermore, the particles displayed excellent long-term stability in solutions of human serum showing no aggregation over a period of 14 days. The functionalized particles also possess multiple reactive surface groups for further coupling reactions. We believe that the surface functionalization schemes described in this report represent a versatile and effective method of stabilizing nanoparticle systems in biological media for their use in a variety of therapeutic and diagnostic applications.
Functional identification of a fatty acid Δ5 desaturase gene from Caenorhabditis elegans (1998)

We have identified a cDNA from the nematode worm Caenorhabditis elegans that encodes a fatty acid delta5 desaturase. Saccharomyces cerevisiae expressing the full-length cDNA was able to convert di-homo-gamma-linolenic acid to arachidonic acid, thus confirming delta5 desaturation. The 1341 bp delta5 desaturase sequence contained an N-terminal cytochrome b5 domain and was located within a kilobase of the C. elegans delta6 desaturase on chromosome IV. With an amino acid identity of 45% it is possible that one of these genes arose from the other by gene duplication. This is the first example of a delta5 desaturase gene isolated from an animal.
A Flexible Synthesis of Azasugars and Homoazasugars via Olefin Metathesis (1997)

A flexible synthesis of azasugars and homoazasugars from vinyl glycine methyl ester is described. The syntheses, which are based on ring closing olefin metathesis steps and stereocontrolled functionalizations of the formed double bonds, offer a broad variability of functionalization and stereochemistry of the products.
New fluorochromes, compatible with high wavelength excitation, for flow cytometric analysis of cellular nucleic acids (1984)

The spectroscopic properties of three new dyes, EK4, VL772, and LL585, free and bound to nucleic acids, are presented, with particular emphasis on their potential use in flow cytometry. Two of these dyes, EK4 and LL585, exhibit red fluorescence, while dye VL772 exhibits yellow fluorescence. Dye LL585 exhibits specificity for DNA, relative to RNA, and a marked enhancement of fluorescence efficiency upon binding to DNA, needed for a red fluorescent DNA-specific stain for flow cytometry. The dye penetrates live cells, although uniformity of nuclear fluorescence, as evidenced by DNA flow histograms, is better if the cells are first permeabilized with Triton X-100. Dye VL772 exhibits yellow fluorescence and little DNA-RNA discrimination, but may prove useful in conjunction with dye LL585 when simultaneous assay of cellular RNA and DNA is desired. Dye EK4 shares properties of the other two dyes but fluoresces with much less efficiency. Dyes LL585 and VL772, used singly, as a pair, or in combination with blue-fluorescing DNA specific dyes, such as bisbenzimidazole derivatives, should permit new, convenient analyses of the content and organization of cellular nucleic acids.
Efficient sequential consistency via conflict ordering (2012)

Although the sequential consistency (SC) model is the most intuitive, processor designers often choose to support relaxed memory consistency models for higher performance. This is because SC implementations that match the performance of relaxed memory models require post-retirement speculation and its associated hardware costs. In this paper we propose an efficient approach for enforcing SC without requiring post-retirement speculation. While prior SC implementations guarantee SC by explicitly completing memory operations within a processor in program order, we guarantee SC by completing conflicting memory operations, within and across processors, in an order that is consistent with the program order. More specifically, we identify those conflicting memory operations whose ordering is critical for the maintenance of SC and explicitly order them. This allows us to safely (non-speculatively) complete memory operations past pending writes, thus reducing memory ordering stalls. Our experiments with SPLASH-2 programs show that SC can be achieved efficiently, with performance comparable to RMO (relaxed memory order).
Optical recording by reducing a metal salt complexed to a polymer host (1984)

An alternative approach which makes use of a laser to reduce a polymer/complexed metal ion matrix to generate small reflective surfaces is described. The thermal energy provided by the laser promotes an electron transfer from the polymer to the metal ion to form metal. Since the reduction occurs within the thermal profile of the focused laser beam, the reflective area has a diameter close to that of the beam waist. We have formed ∼l-μm-diam reflective areas using a pulsed diode laser. Application of this method to optical disk recording is discussed.