gebhart/patrepeval huggingface dataset:
Critical Role for Cd8 in T Cell Receptor Binding and Activation by Peptide/Major Histocompatibility Complex Multimers (2000)

Recent data using MHC/peptide tetramers and dimers suggests that the T cell coreceptors, CD4 and CD8, although important for T cell activation, do not play a direct role in facilitating T cell receptor (TCR) binding to multivalent MHC/peptide ligands. Instead, a current model proposes that coreceptors are recruited only after a stable TCR-MHC/peptide complex has already formed and signaled. In contrast, we show using multimeric class I MHC/peptide ligands that CD8 plays a critical (in some cases obligatory) role in antigen-specific TCR binding. T cell activation, measured by calcium mobilization, was induced by multimeric but not monomeric ligands and also showed CD8 dependency. Our analysis using anti-CD8 antibodies revealed that binding to different epitopes of CD8 can either block or augment TCR-MHC/peptide interaction. These effects on TCR binding to high-affinity agonist ligands were even more pronounced when binding to multimeric low-affinity ligands, including TCR antagonists, was studied. Our data have important implications for the role of CD8 in TCR binding to MHC/peptide ligands and in T cell activation. In addition, our results argue against the view that multimeric MHC/peptide ligands bind directly and solely to the TCR; rather, our data highlight a pivotal contribution of CD8 for this association.
DNA Computation Based Approach for Enhanced Computing Power (2011)

Abstract. DNA computing is a discipline that aims at harnessing individual molecules at the nano-scopic level for computational purposes. Computation with DNA molecules possesses an inherent interest for researchers in computers and biology. Given its vast parallelism and high-density storage, DNA computing approaches are employed to solve many problems. DNA has also been explored as an excellent material and a fundamental building block for building large-scale nanostructures, constructing individual nanomechanical devices, and performing computations. Molecular-scale autonomous programmable computers are demonstrated allowing both input and output information to be in molecular form. This paper presents a review of recent advancements in DNA computing and presents major achievements and challenges for researchers in the coming future.
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism (2018)

The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.
Human umbilical cord wharton's jelly mesenchymal stem cells do not transform to tumor‐associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells (2012)

Human bone marrow mesenchymal stem cells (hBMMSCs) were shown to transform into tumor-associated fibroblasts (TAFs) when in the vicinity of breast cancer tumors and played an important role in tumor enhancement and metastasis. In early human development MSCs migrating from the yolk sac and aorta-gonad-mesonephros (AGM) via the umbilical cord to the placenta and back to the fetal bone marrow were shown to get trapped in the gelatinous Wharton's jelly of the umbilical cord. The common origin of the Wharton's jelly MSCs and the finally homed hBMMSCs prompted us to evaluate whether hWJSCs are also involved in TAF transformation. hWJSCs and hBMMSCs were grown in the presence of breast and ovarian cancer cell conditioned medium (MDA-TCM, TOV-TCM) for 30 days. No changes were observed in the hWJSCs but the hBMMSCs transformed from short to thin long fibroblasts, their proliferation rates increased and CD marker expression decreased. The transformed hBMMSCs showed positive staining for the tumor-associated markers FSP, VEGF, EGF, and Tn-C. Real-time PCR and multiplex luminex bead analysis showed upregulation of TAF-related genes (FSP, FAP, Tn-C, Tsp-1, EGF, bFGF, IL-6, α-SMA, VEGF, and TGF-β) for hBMMSCs with low expression for hWJSCs. The luciferase assay showed that hWJSCs previously exposed to MDA-TCM or TOV-TCM had no stimulatory growth effect on luciferase-tagged MDA or TOV cells unlike hBMMSCs. The results confirmed that hWJSCs do not transform to the TAF phenotype and may therefore not be associated with enhanced growth of solid tumors making them a safe MSC for cell based therapies.
A Simple Unpredictable Pseudo-Random Number Generator (1986)

Two closely-related pseudo-random sequence generators are presented: The ${1 / P}$generator, with input P a prime, outputs the quotient digits obtained on dividing 1 by P. The $x^2 \bmod N$generator with inputs N, $x_0 $ (where $N = P \cdot Q$ is a product of distinct primes, each congruent to 3 mod 4, and $x_0 $ is a quadratic residue $\bmod N$), outputs $b_0 b_1 b_2 \cdots $ where $b_i = {\operatorname{parity}}(x_i )$ and $x_{i + 1} = x_i^2 \bmod N$. From short seeds each generator efficiently produces long well-distributed sequences. Moreover, both generators have computationally hard problems at their core. The first generator’s sequences, however, are completely predictable (from any small segment of $2|P| + 1$ consecutive digits one can infer the “seed,” P, and continue the sequence backwards and forwards), whereas the second, under a certain intractability assumption, is unpredictable in a precise sense. The second generator has additional interesting properties: from knowledge of $x_0 $ and N but notP or Q, one can generate the sequence forwards, but, under the above-mentioned intractability assumption, one can not generate the sequence backwards. From the additional knowledge of P and Q, one can generate the sequence backwards; one can even “jump” about from any point in the sequence to any other. Because of these properties, the $x^2 \bmod N$generator promises many interesting applications, e.g., to public-key cryptography. To use these generators in practice, an analysis is needed of various properties of these sequences such as their periods. This analysis is begun here.
Mesoporous Silica Particles Potentiate Antigen-Specific T-Cell Responses (2014)

The results are promising for the continued development of mesoporous silica materials for therapeutic applications.
An integrated design and characterization environment for the development of a standard cell library (2002)

A design environment is described for the development of a standard cell library. This environment controls a central database called the Cell Data File (CDF). The CDF is a flexible database format for describing a cell technology library. CDF contains all the information necessary to build icon, schematic, and layout views from module generators or custom-crafted cells. Characterization data (transport delays, delay/pf, setup and hold times) can be automatically measured and inserted back in the CDF for translation to logic synthesis timing tables and functional models.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Oral treatment of rats with bovine lactoferrin inhibits carrageenan-induced inflammation; correlation with decreased cytokine production. (1998)

The aim of this study was to investigate an effect of oral treatment of rats with bovine lactoferrin (BLF) on carrageenan-induced inflammation. Rats were given 5 oral doses of BLF (10 mg each) on alternate days and 24 h after the last dose a carrageenan inflammation was induced in the hind foot. Control rats were given 0.9% natrium chloride (NaCl) or bovine serum albumin (BSA). The magnitude of the reaction was measured after 2 h (optimal response) and expressed as an increase of the foot pad thickness in milimeters. The evaluation of BLF effects on carrageenan reaction was supplemented by determination of the ability of spleen cell cultures to produce interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) upon lipopolysaccharide (LPS) induction using bioassays. The results revealed an inhibition of the carrageenan-induced inflammation in BLF-treated rats by 50 and 40% as compared to NaCl and BSA control groups, respectively. The inhibition was also associated with a substantial decrease in the ability of splenocytes to produce IL-6 in BLF-treated rats (94 and 83% as compared to NaCl- and BSA-treated groups). The LPS-induced TNF-alpha production was also decreased, although to a lesser degree (48 and 35%, respectively). The decreased ability of spleen cells to produce inflammatory cytokines in BLF-treated rats indicates that hyporeactivity of the immune system cells may be the basis for the inhibition of carrageenan-induced inflammation.
Tumour-induced angiogenesis: a novel target for drug therapy? (1997)

The ability of a tumour to induce the formation of new blood vessels has a profound effect on tumour growth. The formation of new blood vessels, a process termed angiogenesis, permits rapid expansion of a tumour and increases the risk of metastatic spread. The concept that tumour growth is dependent on the formation of new blood vessels as a source of nutrients and oxygen has stimulated an interest in understanding the basic mechanisms involved in angiogenesis and has formed the basis for a novel therapeutic strategy against cancer. Studies over the past 25 years have begun to elucidate the mechanisms involved in vascular cell proliferation, motility and differentiation leading to the formation of new blood vessels. These studies have unravelled a new array of targets for new drug discovery and therapeutic intervention. A number of molecules that induce angiogenesis and a variety of others that inhibit angiogenesis have been identified. Molecules produced by normal cells that block angiogenesis may be useful in combatting tumour growth, and molecules produced by tumour cells that promote angiogenesis may be useful targets for antitumour drugs. Furthermore, some of the key molecules involved in the process of angiogenesis are also excellent targets for new drug discovery, e.g., the integrin receptors. These laboratory discoveries have now been translated to clinical applications. A number of anti-angiogenesis inhibitors are undergoing clinical trials and new ones are being discovered. Inhibitors of angiogenesis offer the promise of an addition to the current armamentarium of anticancer treatments. Anti-angiogenesis therapy may be useful as an adjunct to chemotherapy, radiation therapy, or surgery. Angiogenesis inhibitors may also have significant benefits because they are likely to have far fewer toxic effects and drug resistance does not appear to be a significant problem. Finally, the same angiogenesis inhibitors developed for anticancer therapy may turn out to be useful for non-neoplastic diseases associated with angiogenesis (e.g., diabetic retinopathy, macular degeneration and arthritis).
Synthesis and spectral studies of 2‐mercapto‐benzimidazole derivatives. II (1983)

Abstract This communication describes synthesis and spectral data of new 2‐mercaptobenzimidazole derivatives.
Preparation of Superconducting YBa2Cu3O7−δ Thin Films by the Dipping-Pyrolysis Process Using Organic Acid Salts (1987)

Abstract Thin films of the superconductor YBa2Cu3O7−δ (YBCO) were prepared on yttria stabilized zirconia (YSZ) substrates by the dipping-pyrolysis process. The starting solution, produced by dissolving barium and copper naphthenates and yttrium stearate into an organic solvent, was coated on the substrates and heated up to 800 °C. Resistivities of the films were measured by the four probe method and superconduction was observed at Tc = 90 K (onset) and 60 K (end).
Translocation of a β-Peptide Across Cell Membranes (2001)

Short cationic peptides derived from DNA-binding proteins, of which HIV Tat is a prototype, can cross the membranes of living cells, and they can bring covalently attached moieties (proteins, drugs) along with them. We show that a beta-amino acid analogue of Tat 47-57 enters HeLa cells with comparable efficiency to Tat 47-57 itself (YGRKKRRQRRR). The beta-peptide is comprised of residues that bear the appropriate side chain at the beta-carbon. Both the alpha- and the beta-peptide were conjugated to fluorescein at the N terminus, and cell penetration was monitored by confocal fluorescence microscopy. Deletion of the three C-terminal arginine residues from the alpha-peptide abolished translocation activity, consistent with prior reports, and deletion of the three C-terminal beta3-homoarginine residues from the beta-peptide had a similarly adverse effect. Thus, alpha- and beta-peptide translocation processes show similar length/charge dependence. The beta-peptide appeared to be largely unfolded in water, which is consistent with the behavior of short Tat-derived alpha-peptides, but in methanol the beta-peptide adopted a helical conformation, in contrast to short Tat-derived alpha-peptides. Our results show that neither altering the oligomeric backbone (amide group spacing) nor increasing the intrinsic propensity to adopt a specific secondary structure affects translocation activity.
Probing Conformational Dynamics of Tau Protein by Hydrogen/Deuterium Exchange Mass Spectrometry (2017)

Fibrillization of the microtubule-associated protein tau has been recognized as one of the signature pathologies of the nervous system in Alzheimer's disease, progressive supranuclear palsy, and other tauopathies. The conformational transition of tau in the fibrillization process, tau monomer to soluble aggregates to fibrils in particular, remains unclear. Here we report on the use of hydrogen/deuterium exchange mass spectrometry (HDX-MS) in combination with other biochemical approaches, including Thioflavin S fluorescence measurements, enzyme-linked immunosorbent assay (ELISA), and Western blotting to understand the heparin-induced tau's fibrillization. HDX-MS studies including anti-tau antibody epitope mapping experiments provided molecular level details of the full-length tau's conformational dynamics and its regional solvent accessibility upon soluble aggregates formation. The results demonstrate that R3 region in the full-length tau's microtubule binding repeat region (MTBR) is stabilized in the aggregation process, leaving both N and C terminal regions to be solvent exposed in the soluble aggregates and fibrils. The findings also illustrate the practical utility of orthogonal analytical methodologies for the characterization of protein higher order structure. Graphical Abstract ᅟ.
Fault tolerant generating and distribution system architecture (1998)

This paper highlights some of the most important minimum requirements for a successful “More Electric” aircraft power generation and distribution system. The need for reliable power electronics is discussed. A new multipurpose power converter concept is introduced along with a powerful new architecture for implementing a more electric fault tolerant generating and distribution system. The possibility of introducing conventional utility ground power for main engine starting is accommodated by the new architecture. (4 pages)
Multi-parametric analysis of cytochrome P450 expression in rat liver microsomes by LA-ICP-MS (2010)

Quantitative analysis of cytochrome P450 (CYP) patterns of cells and tissues is an important aspect in toxicological and pharmacological research as this group of enzymes is largely involved in the metabolism of toxic compounds and drugs. Here we present a method for the multi-parametric and simultaneous quantitative determination of several cytochromes P450 in liver microsomes of untreated and inducer treated rats. The method is based on the binding of specifically lanthanide labelled antibodies to electrophoretically separated and blotted CYP proteins and their subsequent identification and quantification by LA-ICP-MS. CYP1A1, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 were simultaneously quantified and the patterns between microsomal samples were compared. Microsomes of rats treated with 3-methylcholanthrene, phenobarbital and dexamethasone showed increased levels of CYP1A1, CYP2B1 and CYP3A1, respectively. These results coincide with data obtained by independent methods for CYP quantification, i.e.ethoxyresorufinO-deethylase activity for CYP1A1 and pentoxyresorufinO-depentylase for CYP2B1. The presented method is useful for multi-parametric CYP profiling and has further large potential with respect to the number of analysed parameters/proteins and sensitivity.
Preparation and properties of barium sulphate and methyl iothalamate loaded poly(vinyl alcohol) microspheres as radiopaque particulate emboli (1991)

Abstract Poly(vinyl alcohol) (PVA) microspheres impregnated with barium sulphate and methyl iothalamate, having diameters raning from 100 to 1500 μm were prepared by the glutaraldehyde cross‐linking of an aqueous dispersion of PVA containing the radiopaques in paraffin oil using dioctyl sulfosuccinate (DOS) as the stabilizing agent and thionyl chloride as the catalyst. while the use of thionyl chloride allowed the formation of spherical, nonaggregatory beads, other catalysts such as magnesium chloride and hydrochloric acid gave rise to an agglomerated product. The radiopaques were found to be firmly trapped inside the microspheres as they did not leach out on prolonged standing in water, on sonication, or on steam sterilization. Microspheres with pores and channels were also made by incorporating a fine powder of methyl methacrylate along with barium sulphate during their preparation and washing out the polymer after the microspheres were formed. The porous nature of such microspheres was confirmed by transmission electron microscopy (TEM). Microspheres containing the radiopaques exhibited hydrophilicity, swelling ability, and compressibility to a significant extent. the radiopaque nature of the microspheres was confirmed by their x‐ray images. In vitro tests using heparinized calf blood showed that the microspheres were nonhaemolytic in nature. These microspheres may find application as radiopaque emboli in particulate embolization.
Modeling and measurement of optical response of 1D array of metallic nanowires for sensing and detection application (2008)

We have investigated 1D nanosized metallic wires with subwavelength dimensions in which localized surface plasmon (LSP) and surface plasmon polariton (SPP) can exist. Elaboration of the localized surface plasmon resonance (LSPR) based device for scaling down to nanometric dimensions, which provide significant flexible design is the aim of this paper. Modeling of the interaction of the incident light with the periodic system of nanowires (differential formalism) and measurements of the optical (transmittance, extinction) properties of the structures under consideration were performed to reveal the general trends in the design of the gold nanostructure geometry to optimize sensitivity of sensor system.
A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia (2013)

Myeloid differentiation factor 88 (MYD88) L265P somatic mutation is highly prevalent in Waldenström macroglobulinemia (WM) and supports malignant growth through nuclear factor κB (NF-κB). The signaling cascade(s) by which MYD88 L265P promotes NF-κB activation in WM remain unclear. By lentiviral knockdown or use of a MYD88 inhibitor, decreased phosphorylation of the NF-κB gatekeeper IκBα and survival occurred in MYD88 L265P-expressing WM cells. Conversely, WM cells engineered to overexpress MYD88 L265P showed enhanced survival. Coimmunoprecipitation studies identified Bruton tyrosine kinase (BTK) complexed to MYD88 in L265P-expressing WM cells, with preferential binding of MYD88 to phosphorylated BTK (pBTK). Increased pBTK was also observed in WM cells transduced to overexpress L265P vs wild-type MYD88. Importantly, MYD88 binding to BTK was abrogated following treatment of MYD88 L265P-expressing cells with a BTK kinase inhibitor. Inhibition of BTK or interleukin-1 receptor-associated kinase 1 and 4 (IRAK-1 and -4) kinase activity induced apoptosis of WM cells, and their combination resulted in more robust inhibition of NF-κB signaling and synergistic WM cell killing. The results establish BTK as a downstream target of MYD88 L265P signaling, and provide a framework for the study of BTK inhibitors alone, and in combination with IRAK inhibitors for the treatment of WM.
A Blood Pressure Sensor for Long‐Term Implantation (2001)

An implantable flow-through blood pressure sensor prototype has been developed for use with an implantable left ventricular assist device (LVAD). This sensor incorporates a flat pressure-sensing diaphragm that is designed to be integral with the wall of a titanium tube that may be placed in the inlet or the outlet flow path of any LVAD. The interior tube flow geometry is transitioned from a round to a D-shape such that flow separation is eliminated. Bench testing of 3 sensors was performed to characterize the sensor. The worst-case results showed a maximum nonlinearity of 0.64 mm Hg, a maximum hysteresis of 0.87 mm Hg, and a maximum nonrepeatability of 0.87 mm Hg. Long-term drift studies of 2 sensors at 193 days and 112 days resulted in a projected annual drift rate of 1.4 and 2.0 mm Hg, respectively. The APEX pressure sensors were evaluated in 5 ventricular assist acute calf experiments in which the sensor outputs were compared with Millar pressure catheter sensors. Pressure output comparisons showed similar pressure tracings. No visible evidence of thrombus formation was found on the APEX sensor compared with thrombus formation found on the Millar catheter at the entrance to the flow path. Tests demonstrated that the blood pressure sensor can accurately measure blood pressure and indicate that it has long-term stability.
Sub‐10 nm Wide Cellulose Nanofibers for Ultrathin Nanoporous Membranes with High Organic Permeation (2015)

There are increasing requirements for highly efficient and solvent‐resistant nanoporous membranes in various separation processes. Traditional membranes usually have a poor solvent resistance and a thick skin layer leading to a low permeation flux. Currently, the major challenge lies in fabrication of ultrathin few‐nanometers‐pore membranes for fast organic filtration. Herein, a facile approach is presented to prepare ultrafine cellulose nanofibers for fabrication of ultrathin nanoporous membranes. The obtained nanofibers have a uniform diameter of 7.5 ± 2.5 nm and are homogeneously dispersed in aqueous solutions that are favorable to the fabrication of ultrathin nanoporous membranes. The resulting cellulose nanoporous membranes have an adjustable thickness down to 23 nm and pore sizes ranging from 2.5 to 12 nm. They allow fast permeation of water and organics during pressure‐driven filtration. Typically, the 30 nm thick membrane has high fluxes of 1.14 and 3.96 × 10 4 L h −1 m −2 bar −1 for pure water and acetone respectively. Furthermore, the as‐prepared cellulose nanofibers are easily employed to produce a novel syringe filter with sub‐10 nm pores that have a wide application in fast separation and purification of nanoparticles on few‐nanometers scale.