gebhart/patrepeval huggingface dataset:
Human Toll-Like Receptors Mediate Cellular Activation by Mycobacterium tuberculosis (1999)

Recent studies have implicated a family of mammalian Toll-like receptors (TLR) in the activation of macrophages by Gram-negative and Gram-positive bacterial products. We have previously shown that different TLR proteins mediate cellular activation by the distinct CD14 ligands Gram-negative bacterial LPS and mycobacterial glycolipid lipoarabinomannan (LAM). Here we show that viable Mycobacterium tuberculosis bacilli activated both Chinese hamster ovary cells and murine macrophages that overexpressed either TLR2 or TLR4. This contrasted with Gram-positive bacteria and Mycobacterium avium, which activated cells via TLR2 but not TLR4. Both virulent and attenuated strains of M. tuberculosis could activate the cells in a TLR-dependent manner. Neither membrane-bound nor soluble CD14 was required for bacilli to activate cells in a TLR-dependent manner. We also assessed whether LAM was the mycobacterial cell wall component responsible for TLR-dependent cellular activation by M. tuberculosis. We found that TLR2, but not TLR4, could confer responsiveness to LAM isolated from rapidly growing mycobacteria. In contrast, LAM isolated from M. tuberculosis or Mycobacterium bovis bacillus Calmette-Guérin failed to induce TLR-dependent activation. Lastly, both soluble and cell wall-associated mycobacterial factors were capable of mediating activation via distinct TLR proteins. A soluble heat-stable and protease-resistant factor was found to mediate TLR2-dependent activation, whereas a heat-sensitive cell-associated mycobacterial factor mediated TLR4-dependent activation. Together, our data demonstrate that Toll-like receptors can mediate cellular activation by M. tuberculosis via CD14-independent ligands that are distinct from the mycobacterial cell wall glycolipid LAM.
Diffusion barrier properties of tungsten nitride films grown by atomic layer deposition from bis(tert-butylimido)bis(dimethylamido)tungsten and ammonia (2003)

Highly uniform, smooth, and conformal coatings of tungsten nitride (WN) were synthesized by atomic layer deposition (ALD) from vapors of bis(tert-butylimido)bis(dimethylamido)tungsten and ammonia. The films are shiny, silver colored, and electrically conducting. The films were amorphous as deposited. 100% step coverage was obtained inside holes with aspect ratios greater than 40:1. WN films as thin as 1.5 nm proved to be good barriers to diffusion of copper for temperatures up to 600 °C. Annealing for 30 min at temperatures above 725 °C converted the WN to pure, polycrystalline tungsten metal. ALD of copper onto the surface of the WN produced strongly adherent copper films that could be used as “seed” layers for chemical vapor deposition or electrodeposition of thicker copper coatings.
Folate-Binding Proteins (1990)

Folate-binding proteins of three major classes have been observed in various bodily fluids and in the plasma membrane and cytoplasm of normal and neoplastic cells. A major class, the high-affinity folate-binding proteins, show a preferential and tight binding of folic acid relative to reduced folates and methotrexate and consist of water-soluble and membrane-associated forms. Soluble forms of the high-affinity binders are present in serum and milk and in the growth medium of certain cultured cell lines, whereas membrane-associated forms are observed on the surface of various cells and tissues. The binders in serum have no clearly defined function, whereas the milk binders serve to accumulate and stabilize reduced-folate compounds in milk and they may also facilitate the absorption of folates by the intestinal mucosa of neonates. Membrane-bound forms of high-affinity folate-binding proteins mediate the transport of folate compounds across plasma membranes and appear to utilize endocytosis as the transport mechanism. Membrane-associated high-affinity binding proteins contain covalently bound phospholipids and hydrophobic C-terminal amino acid sequences that are absent in the soluble forms. The remaining protein portions of these binders show considerable sequence homology. The second class is composed of folate-binding proteins that reside solely in the plasma membrane and are structurally and mechanistically distinct from the high-affinity binders. These proteins function in transport, exhibit varied substrate specificities that accommodate reduced-folate compounds with equal or higher affinity than folate, and do not utilize endocytosis as the mechanism for substrate internalization. The third class of folate-binding proteins consists of enzymes that reside in the cytoplasm of cells.
A Peptide Found in Schizophrenia and Autism Causes Behavioral Changes in Rats (1999)

In a previous study we showed that β-casomorphin-7 (β-CM7) is taken up by brain regions relevant to schizophrenia and autism. The present experiment was designed to find whether β-CM7 has any behavioral or analgesic effects in rats. About 65 seconds after treatment with different doses of β-CM7, rats became restless and ran violently, with teeth chattering and with rapid respiration. Seven minutes later, the rats became inactive with less walking, distancing themselves from the other rat in the same cage, and sitting in, or putting their head against, the corner of the cage. The sound response was reduced and social interaction was absent. One hour later, the rats showed hyperdefensiveness. The above behavioral effects of β-CM7 did not occur when rats were pretreated with naloxone (2 mg/kg, IP). The rats receiving saline did not show any behavioral changes throughout the 2 hour period of observation. β-CM7 also demonstrated analgesic effects, which could be blocked by naloxone. The results suggest that β-CM7 may play a role in behavioral disorders such as autism and schizophrenia.
PEGylation of Nanosubstrates (Titania) with Multifunctional Reagents: At the Crossroads between Nanoparticles and Nanocomposites (2012)

Titania (anatase) nanoparticles were successfully PEGylated through the use of catechol (dopamine)-terminated PEG derivatives. The resulting materials were characterized by excellent stability at neutral pH and extremely low toxicity (phagocytic and nonphagocytic cell lines). In particular, we focused on the comparison between mono- and bis-catechol PEGs. Due to the double terminal anchorage on the titania surface, bis-catechol ligands can produce chains differing from classical monoanchored PEG in conformation (horseshoe-shaped vs brush) and thus the possibility of interactions with biomolecules. At the same time, less than quantitative catechol binding may lead to the presence of dangling chains with unbound catechols which can polymerize and eventually produce PEG/titania nanocomposite colloids. Our results on double-functional PEG2000 show the latter to be the case. Pluronic F127 was also used as a bifunctional ligand, leading to nanocomposite aggregates with an even larger organic content.
Synthesis of Novel 5-Substituted 3-Amino-3,4-dihydro-2H-1-benzopyran Derivatives and Their Interactions with the 5-HT1A Receptor (2000)

A series of new enantiomerically pure 3-amino-3,4-dihydro-2H-1-benzopyrans (3-aminochromans) has been synthesized from (R)- and (S)-5-methoxy-3-amino-3,4-dihydro-2H-1-benzopyran. The absolute configuration of the respective (R)- and (S)-enantiomers was deduced from X-ray crystallography of (R)-3-(N-isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran, (R)-9a. Various 5-substituents were introduced via palladium-catalyzed carbonylation of N-substituted 3-amino-5-trifluoromethanesulfonyloxy-3,4-dihydro-2H-1-benzopyran. The effect of N- and 5-substitution on affinity for the 5-HT1A receptor was evaluated in competition experiments using rat hippocampal membranes and [3H]8-OH-DPAT as radioligand. Selected compounds were also tested for their affinity to the D1 (rat striatum), D2 (rat striatum), D2A (human cloned), and 5-HT2A (rat cortex) receptors. The intrinsic activity of the compounds was evaluated by measuring their effect on VIP-stimulated cAMP production in GH4ZD10 cells stably transfected with the 5-HT1A receptor. High-affinity compounds with high selectivity for the 5-HT1A receptor were found among structures substituted with carboxylate esters, amides, and ketones in the 5-position. Primary and secondary amines bound with lower affinity than tertiary amines. Larger substituents were well-tolerated by the receptor, but the smaller N-ethyl-N-isopropyl bound with lower affinity. Generally, the (R)-enantiomers displayed higher affinity for the 5-HT1A receptor than the corresponding (S)-enantiomers. In the present series of compounds, both full and partial agonists were found.
Binding, migration, and scalability in CORBA (1998)

x x x x x x x x x x x x x x x x Apart from the ability to denote remote objects and to convert to and from strings, CORBA references have semantics that are very similar to those of C++ class pointers: references can dangle (point at a nonexistent or unreachable object) and they can be nil (contain a special value that indicates a reference pointing nowhere).
Enantioselective Synthesis of Cyclic Secondary Amines through Mo-Catalyzed Asymmetric Ring-Closing Metathesis (ARCM) (2003)

Carbocyclic amines are synthesized efficiently in up to 93% ee by asymmetric ring-closing metathesis (ARCM) with 2-5 mol % chiral Mo complexes. An example is provided where the catalyst is prepared in situ (catalyst isolation not needed) to afford secondary amines that cannot be prepared by alternative methods. [reaction: see text]
Ouabain Resistance Conferred by Expression of the cDNA for a Murine Na + , K + -ATPase α Subunit (1987)

The molecular basis for the marked difference between primate and rodent cells in sensitivity to the cardiac glycoside ouabain has been established by genetic techniques. A complementary DNA encoding the entire alpha 1 subunit of the mouse Na+- and K+-dependent adenosine triphosphatase (ATPase) was inserted into the expression vector pSV2. This engineered DNA molecule confers resistance against 10(-4) M ouabain to monkey CV-1 cells. Deletion of sequences encoding the carboxyl terminus of the alpha 1 subunit abolish the activity of the complementary DNA. The ability to assay the biological activity of this ATPase in a transfection protocol permits the application of molecular genetic techniques to the analysis of structure-function relationships for the enzyme that establishes the internal Na+/K+ environment of most animal cells. The full-length alpha 1 subunit complementary DNA will also be useful as a dominant selectable marker for somatic cell genetic studies utilizing ouabain-sensitive cells.
Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. (1992)

Cytomegalovirus (CMV) is a major cause of inflammatory organ disease in immunosuppressed persons. To elucidate the mechanisms of CMV-induced inflammation, we investigated whether tumor necrosis factor-alpha (TNF-alpha) was involved in the pathogenesis of CMV colitis in patients with AIDS. In in situ hybridization experiments, TNF-alpha mRNA was shown to be abundantly present in colonic mucosa from AIDS patients with CMV colitis but not in colonic mucosa from control (AIDS and normal) subjects. The TNF-alpha transcripts, identified in macrophage-like cells containing cytomegalic inclusions, were positively associated with CMV, but not HIV-1, within the mucosa. In in vitro experiments, a patient-derived isolate of CMV, but not HIV-1Ba-L, induced human monocytes to express TNF-alpha mRNA and to release increased levels of TNF-alpha peptide following stimulation. CMV induction of TNF-alpha may play a critical role in CMV-induced inflammation and, since TNF-alpha upregulates expression of HIV-1, offers a mechanism by which CMV could serve as a co-factor for HIV-1 expression without both viruses infecting the same cell.
In Vitro Investigations on the Toxicity and Cell Death Induced by Tamoxifen on Two Non‐Breast Cancer Cell Types (2001)

Tamoxifen, a potent anticancer agent known to interrupt the enhanced estrogen activity of malignant mammary gland cells, was recently approved by the Food and Drug Administration (FDA)for the treatment of breast cancer. In this investigation, the toxic effects of tamoxifen were evaluated through cell multiplication, and cytological, surface ultrastructural, and biochemical studies on human cervical carcinoma cells (HeLa)and/or murine erythroleukemic (MEL) cells (BB-88). Tamoxifen treatment demonstrated an inhibitory effect on HeLa cell multiplication at lower concentrations and toxicity at higher concentrations and longer treatment durations. The drug also triggered morphological and biochemical changes as revealed by light microscopy, scanning electron microscopy (SEM), fluorescence microscopy, Nucleosome ELISA, and the DNA smear pattern. Cytological observations showed nuclear condensation, cell shrinkage, multinucleation, and apoptotic bodies. Surface ultrastructure of tamoxifen treated cells examined under the SEM revealed abnormalities such as membrane blebbing, holes, and cytoplasmic extrusions, all of which are characteristics of programmed cell death (apoptosis). Redistribution of the membrane phospholipid phosphatidylserine (PS) from the protoplasmic surface of the plasma membrane to the cell surface was identified using annexin V-enhanced green fluorescent protein (EGFP) in tamoxifen treated MEL BB-88 cells, a general feature of cells undergoing apoptosis. Tamoxifen treated cells demonstrated internucleosomal damages of the genomic DNA and DNA fragmentations, evidenced by an increase in free nucleosomes, and distinctive DNA smear patterns on the agarose gel.
Long-term vaginal antibody delivery: Delivery systems and biodistribution (2000)

Topical delivery systems can provide prolonged delivery of antibodies to the vaginal mucosal surface for long-term protection against infectious diseases. We examined the biodistribution of antibodies during 30 days of vaginal antibody delivery in mice. Different antibody preparations (including monoclonal IgG and IgM, as well as several different (125)I-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide continuous antibody delivery. Antibody concentrations remained high in the vaginal secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at approximately 100 times lower concentration, in the blood and other tissues. The measured concentrations agreed reasonably well with a simple pharmacokinetic model, which was used to calculate mucosal and systemic concentrations as a function of antibody delivery and elimination rates. Results from the model were consistent with previously reported antibody pharmacokinetic measurements: the half-life for antibody elimination for the vagina was approximately 3 h; the half-life for IgG(1) clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was approximately 0.01 to 0.03 h(-1). These results provide important information for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, long-term vaginal administration of antibodies may be a reasonable approach for achieving sustained mucosal and systemic antibody levels.
Public private partnerships: Improving the science of public procurement (2007)

Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for lithium in the regulation of inflammation, oxidative stress, and neurodegeneration <i>albeit</i> unclear about its exact mode of action. Thus, the intention of this study is to delineate the regulatory mechanisms of lithium on oxidative stress in lipopolysaccharide- (LPS-) activated macrophages by evaluating its effects on nuclear factor-<i>κ</i>B (NF-<i>κ</i>B) activity and mRNA expression of multiple oxidative stress-related NF-<i>κ</i>B genes. Raw 264.7 macrophages were treated with up to 10 mM lithium, and no change in cell proliferation, viability, growth, and cell adhesion was observed in real time. Pretreatment with low doses of lithium was shown to reduce nitric oxide (NO) production in LPS-activated macrophages. A reduced internal H<sub>2</sub>DCFDA fluorescence intensity, indicative of reduced reactive oxygen species (ROS) production, was observed in LPS-activated Raw 264.7 macrophages treated with lithium. Lithium has been shown to lower the production of the chemokine RANTES; furthermore, this inhibitory action of lithium has been suggested to be independent of glycogen synthase kinase-3 <i>β</i> (GSK3<i>β</i>) activity. It is shown here that lithium modulates the expression of several inflammatory genes including I<i>κ</i>B-<i>α</i>, TRAF3, Tollip, and NF-<i>κ</i>B1/p50 which are regulators of the NF-<i>κ</i>B pathway. Moreover, lithium inhibits NF-<i>κ</i>B activity by lowering nuclear translocation of NF-<i>κ</i>B in LPS-activated macrophages. This is the first study to associate Tollip, Traf-3, and I<i>κ</i>B-<i>α</i> mRNA expression with lithium effect on NF-<i>κ</i>B activity in LPS-activated Raw 264.7 macrophages. Although these effects were obtained using extratherapeutic concentrations of lithium, results of this study provide useful information towards understanding the mode of action of lithium. This study associates lithium with reduced oxidative stress in LPS-activated Raw 264.7 macrophages and further suggests candidate molecular targets for the regulation of oxidative stress-related diseases using lithium beyond bipolar disorders.
Carboxypeptidase M Activity Is Increased in Bronchoalveolar Lavage in Human Lung Disease (1995)

Carboxypeptidase M (CPM) cleaves the C-terminal arginine and lysine of peptides; it is expressed in the lung, especially on the plasma membrane of alveolar type I cells. Here, we report on CPM in human bronchoalveolar lavage (BAL) collected from 69 patients and analyzed for activity, cell number and type, and protein level. Seventy-six percent of CPM activity, measured at pH 7.5 with 5-dimethylamino-naphthalene-1-sulfonyl-alanyl-arginine (Dansyl-Ala-Arg) substrate, was immunoprecipitated with polyclonal antibody to purified human enzyme. In patients without active lung disease, CPM activity in BAL was 7.69 (+/- 2.12) nmol/h/mg protein, but in patients with acute pneumonia, it was 29.25 (+/- 4.06) (p < 0.01). In patients with Pneumocystis carinii pneumonia, CPM activity was elevated to 26.00 (+/- 4.85) (p < 0.01) and in patients with lung cancer, to 30.95 (+/- 4.12) (p < 0.01). The activity was not associated with the cellular elements of BAL. The highest specific activity was in the large aggregate fraction of surfactant, which also contained the highest concentration of phosphorus. Transmission electron microscopy of this fraction revealed the presence of typical lamellar bodies and tubular myelin structures. The high CPM activity may stem from its induction and release in acute lung disease. In addition, CPM may be a marker of infection with certain pathogens and an indicator of type I cell injury in parenchymal lung diseases.
Electrostatic Imprint Process for Glass (2008)

In usual thermal imprint process, mold patterns are transferred by applying mechanical pressures at elevated temperatures. We have developed a new imprint process for glass, which utilizes electrostatic force as a driving force for deformation. In the method, high dc voltage is applied between a mold and a glass specimen so that the mold becomes an anode. This method enables glass forming at lower temperatures with smaller mechanical force compared to usual thermal imprint process. In addition, this method is suitable for small patterns less than 1 µm. It is expected that this method realizes large-area and high-efficiency nano-forming process for glass.
Learning to Track: Conceptual Manifold Map for Closed-Form Tracking (2005)

Our objective is to model the visual manifold of object appearance corresponding to geometric transformation. We learn a generative model for object appearance where the appearance of the object at each new frame is a function that maps from a conceptual representation of the geometric transformation space into the visual manifold. By learning such generative model we can infer the geometric transformation (track) directly from the tracked object appearance. As a result tracking can be achieved in a closed form and therefore can be done very efficiently.
Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia (2009)

These data suggest that fibrils and oligomers stimulate unique signaling responses in microglia leading to discrete secretory changes and effects on neuron survival. This suggests that inflammation changes during disease may be the consequence of unique peptide-stimulated events and each conformation may represent an individual anti-inflammatory therapeutic target.
Host organ specifically determines cancer progression. (1995)

In order to further understand the role of the host organ in tumor progression, we have transplanted into nude mice histologically intact human colon cancer tissue on the serosal layers of the stomach (heterotopic site) and the serosal layers of the colon (orthotopic site). Xenograft lines Co-3, which is well differentiated, and poorly differentiated COL-3-JCK were used for transplantation. After orthotopic transplantation of the human colon tumors on the nude mouse colon, the growing colon tumor resulted in macroscopically extensive invasive local growth in 4 of 10 mice, serosal spreading in 9 of 10 mice, musclaris propria invasion in 1 of 10 mice, submucosal invasion in 3 of 10 mice, mucosal invasion in 3 of 10 mice, lymphatic duct invasion in 4 of 10 mice, regional lymph node metastasis in 4 of 10 mice, and liver metastasis in 1 of 10 mice. In striking contrast, after heterotopic transplantation of the human colon tumor on the nude mouse stomach, a large growing tumor resulted but with only limited invasive growth and without serosal spreading, lymphatic duct invasion, or regional lymph node metastasis. It has become clear from these studies that the orthotopic site, in particular the serosal and subserosal transplant surface, is critical to the growth, spread, and invasive and metastatic capability of the implanted colon tumor in nude mice. These studies suggest that the original host organ plays the same critical role in tumor progression.
Usefulness of alirocumab and evolocumab for the treatment of patients with diabetic dyslipidemia (2018)

In 2015, the US Food and Drug Administration (FDA) approved the anti-proprotein convertase subtilsin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, to treat patients with hypercholesterolemia and mixed dyslipidemia. Since then, considerable attention has been paid to the use of these monoclonal antibodies for the treatment of diabetic dyslipidemia with a goal of reducing the risk for cardiovascular disease. Recently, consensus statements on the clinical use of PCSK9 inhibitors in patients with type 2 diabetes mellitus, who are unable to achieve the goal of low-density lipoprotein cholesterol (<70 mg/dL or <1.8 mmol/L), have been published by panels of experts in Greece, Europe (European Society of Cardiology and European Atherosclerosis Society Task Force), and the United States (American College of Cardiology Consensus Committee). On December 1, 2017, the FDA approved evolocumab to prevent heart attack, stroke, and coronary revascularization. In this article, we review recent advances concerning the pathophysiology of diabetic dyslipidemia, the physiology of PCSK9, the mechanisms of action of PCSK9 inhibitors, clinical trials examining PCSK9 inhibitors in type 2 diabetes, and perspectives of nonstatin therapy in the treatment of diabetic dyslipidemia.