gebhart/patrepeval huggingface dataset:
Protection of human breast cancer cells from complement-mediated lysis by expression of heterologous CD59 (1999)

CD59, decay accelerating factor (DAF) and membrane cofactor protein (MCP) are widely expressed cell surface glycoproteins that protect host cells from the effects of homologous complement attack. Complement inhibitory activity of these proteins is species-selective. We show that the human breast cancer cell line MCF7 is relatively resistant to lysis by human complement, but is effectively lysed by rat or mouse complement. CD59, DAF and MCP were all shown to be expressed by MCF7. The species-selective nature of CD59 activity was used to demonstrate directly the effectiveness of CD59 at protecting cancer cells from complement-mediated lysis. cDNAs encoding rat and mouse CD59 were separately transfected into MCF7 cells, and cell populations expressing high levels of the rodent CD59 were isolated by cell sorting. Data show that rat and mouse CD59 were highly effective at protecting transfected MCF7 cells from lysis by rat and mouse complement, respectively. Data further reveal that rat CD59 is not effective against mouse complement, whereas mouse CD59 is effective against both mouse and rat complement. These studies establish a model system for relevant in vivo studies aimed at determining the effect of complement regulation on tumourigenesis, and show that for effective immunotherapy using complement-activating anti-tumour antibodies, the neutralization of CD59 and/or other complement inhibitory molecules will probably be required.
The contribution of epigenetics in SjÃ¶grenâ€™s Syndrome (2014)

Sjögren's syndrome (SS) is a chronic autoimmune epithelitis that combines exocrine gland dysfunctions and lymphocytic infiltrations. While the pathogenesis of SS remains unclear, its etiology is multifunctional and includes a combination of genetic predispositions, environmental factors, and epigenetic factors. Recently, interest has grown in the involvement of epigenetics in autoimmune diseases. Epigenetics is defined as changes in gene expression, that are inheritable and that do not entail changes in the DNA sequence. In SS, several epigenetic mechanisms are defective including DNA demethylation that predominates in epithelial cells, an abnormal expression of microRNAs, and abnormal chromatin positioning-associated with autoantibody production. Last but not least, epigenetic modifications are reversible as observed in minor salivary glands from SS patients after B cell depletion using rituximab. Thus epigenetic findings in SS open new perspectives for therapeutic approaches as well as the possible identification of new biomarkers.
Key Management for Multicast: Issues and Architectures (1999)

This report contains a discussion of the difficult problem of key management for multicast communication sessions. It focuses on two main areas of concern with respect to key management, which are, initializing the multicast group with a common net key and rekeying the multicast group. A rekey may be necessary upon the compromise of a user or for other reasons (e.g., periodic rekey). In particular, this report identifies a technique which allows for secure compromise recovery, while also being robust against collusion of excluded users. This is one important feature of multicast key management which has not been addressed in detail by most other multicast key management proposals The benefits of this proposed technique are that it minimizes the number of transmissions required to rekey the multicast group and it imposes minimal storage requirements on the multicast group.
Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape (2012)

Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab) responses as early as 2 weeks post-seroconversion, with Nab titers as low as 1∶20 to 1∶50 (IC(50)) selecting for virus escape. In each of the subjects, Nabs targeted different regions of the HIV-1 envelope (Env) in a strain-specific, conformationally sensitive manner. In subject CH40, virus escape was first mediated by mutations in the V1 region of the Env, followed by V3. HIV-1 specific monoclonal antibodies from this subject mapped to an immunodominant region at the base of V3 and exhibited neutralizing patterns indistinguishable from polyclonal antibody responses, indicating V1-V3 interactions within the Env trimer. In subject CH77, escape mutations mapped to the V2 region of Env, several of which selected for alterations of glycosylation. And in subject CH58, escape mutations mapped to the Env outer domain. In all three subjects, initial Nab recognition was followed by sequential rounds of virus escape and Nab elicitation, with Nab escape variants exhibiting variable costs to replication fitness. Although delayed in comparison with autologous CD8 T-cell responses, our findings show that Nabs appear earlier in HIV-1 infection than previously recognized, target diverse sites on HIV-1 Env, and impede virus replication at surprisingly low titers. The unexpected in vivo sensitivity of early transmitted/founder virus to Nabs raises the possibility that similarly low concentrations of vaccine-induced Nabs could impair virus acquisition in natural HIV-1 transmission, where the risk of infection is low and the number of viruses responsible for transmission and productive clinical infection is typically one.
Chronically Impaired Autoregulation of Cerebral Blood Flow in Long-Term Diabetics (1975)

Using the arteriovenous oxygen difference method autoregulation of cerebral blood flow (CBF) was tested in 16 long-term diabetics and eight control patients. Blood pressure was raised by angiotensin infusion and lowered by trimethaphan camsylate infusion, in some cases combined with head-up tilting of the patient. Regression analysis was carried out on the results in order to quantify autoregulatory capacity. In the control patients CBF did not vary with moderate blood pressure variations, indicating normal autoregulation. In four of the 16 diabetic patients CBF showed significant pressure dependency, indicating impaired autoregulation. The cause of impaired autoregulation in some long-term diabetics is believed to be diffuse or multifocal dysfunction of cerebral arterioles due to diabetic vascular disease. Other conditions with impaired autoregulation are discussed and compared with that seen in long-term diabetes.
Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP (2009)

A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices.
A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions (2006)

Tandem affinity strategies reach exceptional protein purification grades and have considerably improved the outcome of mass spectrometry-based proteomic experiments. However, current tandem affinity tags are incompatible with two-step purification under fully denaturing conditions. Such stringent purification conditions are desirable for mass spectrometric analyses of protein modifications as they result in maximal preservation of posttranslational modifications. Here we describe the histidine-biotin (HB) tag, a new tandem affinity tag for two-step purification under denaturing conditions. The HB tag consists of a hexahistidine tag and a bacterially derived in vivo biotinylation signal peptide that induces efficient biotin attachment to the HB tag in yeast and mammalian cells. HB-tagged proteins can be sequentially purified under fully denaturing conditions, such as 8 m urea, by Ni(2+) chelate chromatography and binding to streptavidin resins. The stringent separation conditions compatible with the HB tag prevent loss of protein modifications, and the high purification grade achieved by the tandem affinity strategy facilitates mass spectrometric analysis of posttranslational modifications. Ubiquitination is a particularly sensitive protein modification that is rapidly lost during purification under native conditions due to ubiquitin hydrolase activity. The HB tag is ideal to study ubiquitination because the denaturing conditions inhibit hydrolase activity, and the tandem affinity strategy greatly reduces nonspecific background. We tested the HB tag in proteome-wide ubiquitin profiling experiments in yeast and identified a number of known ubiquitinated proteins as well as so far unidentified candidate ubiquitination targets. In addition, the stringent purification conditions compatible with the HB tag allow effective mass spectrometric identification of in vivo cross-linked protein complexes, thereby expanding proteomic analyses to the description of weakly or transiently associated protein complexes.
Fatal outcome after ethanol renal ablation in child with end-stage kidneys (1986)

Fatal outcome after ethanol renal ablation in child with end-stage kidneysL Garel, JL Mareschal, MF Gagnadoux, D Pariente, M Guilbert and J SauvegrainAudio Available | Share
Agarose-stabilized gold nanoparticles for surface-enhanced Raman spectroscopic detection of DNA nucleosides (2006)

We present surface-enhanced Raman scattering (SERS) studies of DNA nucleosides using biologically benign agarose-stabilized gold nanoparticles (AAuNP). We compare the SERS activity of nucleosides with AAuNP to that of commercially obtained citrate-stabilized gold nanoparticles and find the SERS activity to be an order of magnitude higher with AAuNP. The higher SERS activity is explained in terms of the agarose matrix, which provides pathways for the gold nanoparticles to have distinct arrangements that result in stronger internal plasmon resonances.
Human Peripheral Blood Cells Differentially Recognize and Respond to Two Distinct CpG Motifs (2001)

Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN. One cluster ("D") preferentially stimulates IFN-gamma production by NK cells, whereas the other ("K") stimulates cell proliferation and the production of IL-6 and IgM by monocytes and B cells. The distinct immunostimulatory properties of K and D ODN can improve the design of CpG-based products to achieve specific therapeutic goals.
Ultraviolet-to-blue color-converting scintillating-fibers photoreceiver for 375-nm laser-based underwater wireless optical communication (2019)

Underwater wireless optical communication (UWOC) can offer reliable and secure connectivity for enabling future internet-of-underwater-things (IoUT), owing to its unlicensed spectrum and high transmission speed. However, a critical bottleneck lies in the strict requirement of pointing, acquisition, and tracking (PAT), for effective recovery of modulated optical signals at the receiver end. A large-area, high bandwidth, and wide-angle-of-view photoreceiver is therefore crucial for establishing a high-speed yet reliable communication link under non-directional pointing in a turbulent underwater environment. In this work, we demonstrated a large-area, of up to a few tens of cm<sup>2</sup>, photoreceiver design based on ultraviolet(UV)-to-blue color-converting plastic scintillating fibers, and yet offering high 3-dB bandwidth of up to 86.13 MHz. Tapping on the large modulation bandwidth, we demonstrated a high data rate of 250 Mbps at bit-error ratio (BER) of 2.2 × 10<sup>-3</sup> using non-return-to-zero on-off keying (NRZ-OOK) pseudorandom binary sequence (PRBS) 2<sup>10</sup>-1 data stream, a 375-nm laser-based communication link over the 1.15-m water channel. This proof-of-concept demonstration opens the pathway for revolutionizing the photodetection scheme in UWOC, and for non-line-of-sight (NLOS) free-space optical communication.
Utility of in vitro culture to the study of plant mitochondrial genome configuration and its dynamic features (2012)

Recombination activity plays an important role in the heteroplasmic and stoichiometric variation of plant mitochondrial genomes. Recent studies show that the nuclear gene MSH1 functions to suppress asymmetric recombination at 47 repeat pairs within the Arabidopsis mitochondrial genome. Two additional nuclear genes, RECA3 and OSB1, have also been shown to participate in the control of mitochondrial DNA exchange in Arabidopsis. Here, we demonstrate that repeat-mediated de novo recombination is enhanced in Arabidopsis and tobacco mitochondrial genomes following passage through tissue culture, which conditions the MSH1 and RECA3 suppressions. The mitochondrial DNA changes arising through in vitro culture in tobacco were reversible by plant regeneration, with correspondingly restored MSH1 transcript levels. For a growing number of plant species, mitochondrial genome sequence assembly has been complicated by insufficient information about recombinationally active repeat content. Our data suggest that passage through cell culture provides a rapid and effective means to decipher the dynamic features of a mitochondrial genome by comparative analysis of passaged and non-passaged mitochondrial DNA samples following next-generation sequencing and assembly.
Structure-activity analyzed by pattern recognition: the asymmetric case (1980)

In classification studies in which pattern-recognition methods are used to distinguish active compounds from inactive ones, a type of data structure which we call "asymmetric" can be observed. This type of data structure can be quite common and its occurrence can have a profound effect on the classification analysis outcome. The origin of asymmetric data structure and a strategy or obtaining meaningful classification results when it is observed are discussed and illustrated with an example of active and inactive antimalarial quinones.
Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells (2002)

We have derived from normal human, mouse, and rat postnatal bone marrow primitive, multipotent adult progenitor cells (MAPCs) that can differentiate into most mesodermal cells and neuroectodermal cells in vitro and into all embryonic lineages in vivo. Here, we show that MAPCs can also differentiate into hepatocyte-like cells in vitro. Human, mouse, and rat MAPCs, cultured on Matrigel with FGF-4 and HGF, differentiated into epithelioid cells that expressed hepatocyte nuclear factor-3beta (HNF-3beta), GATA4, cytokeratin 19 (CK19), transthyretin, and alpha-fetoprotein by day 7, and expressed CK18, HNF-4, and HNF-1alpha on days 14-28. Virtually all human, as well as a majority of rodent cells stained positive for albumin and CK18 on day 21; 5% (rodent) to 25% (human) cells were binucleated by day 21. These cells also acquired functional characteristics of hepatocytes: they secreted urea and albumin, had phenobarbital-inducible cytochrome p450, could take up LDL, and stored glycogen. MAPCs, which can be expanded in vitro and maintained in an undifferentiated state for more than 100 population doublings, can thus differentiate into cells with morphological, phenotypic, and functional characteristics of hepatocytes. MAPCs may therefore be an ideal cell for in vivo therapies for liver disorders or for use in bioartificial liver devices.
An inner product space approach to image coding by contractive transformations (1991)

Consideration is given to modeling of arbitrary digital gray tone images as the fixed points of contractive transformations on the image space. The transformation is designed to exploit a form of image redundancy called piecewise self-similarity. Results from inner product space theory are used to optimize the transformation within a class of affine transformations. The resulting transformation is described by a small amount of information compared to the original image, and its piecewise self-similar fixed point, found by successively iterating the transformation from any initial image, is close to the original image. Results are improved compared to earlier results with this technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Compression Artifacts Reduction by a Deep Convolutional Network (2015)

Lossy compression introduces complex compression artifacts, particularly the blocking artifacts, ringing effects and blurring. Existing algorithms either focus on removing blocking artifacts and produce blurred output, or restores sharpened images that are accompanied with ringing effects. Inspired by the deep convolutional networks (DCN) on super-resolution, we formulate a compact and efficient network for seamless attenuation of different compression artifacts. We also demonstrate that a deeper model can be effectively trained with the features learned in a shallow network. Following a similar "easy to hard" idea, we systematically investigate several practical transfer settings and show the effectiveness of transfer learning in low level vision problems. Our method shows superior performance than the state-of-the-arts both on the benchmark datasets and the real-world use cases (i.e. Twitter).
Reverse Physiology: Discovery of the Novel Neuropeptide, Orphanin FQ/Nociceptin (1998)

The search for novel neurotransmitters and neuropeptides has been recently revolutionized by the development of a purification strategy based on orphan G protein-coupled receptors, cloned receptors for which no natural ligands are known. This strategy uses the orphan receptor as bait to identify its natural ligand. This article will review the discovery of the first natural ligand isolated following this strategy. This ligand is a peptide that shares some striking sequence similarity to the opioid peptides and has been named Orphanin FQ or Nociceptin (OFQ/NOC). The discovery of OFQ/NOC will be described as one example of the use of orphan receptors in identifying novel neurotransmitters and neuropeptides, an example that has already been followed in the identification of other novel neuropeptides. After reviewing the conceptual and technological basis of the strategy and its successful first application, we discuss the criteria used to validate OFQ/NOC as the natural ligand of the orphan receptor and as a genuine neuropeptide. We also discuss the importance and implications of discovering OFQ/NOC mode of synthesis, which is synthesized as expected in the form of a larger polypeptide precursor, which in turn raises the question of the existence of other OFQ/NOC-related peptides. We then present an overview of the numerous studies that have blossomed after the OFQ/NOC discovery and describe the numerous physiological roles that have already been attributed to OFQ/NOC, and in particular the controversy regarding its involvement in pain perception. Because of the similarities between the OFQ/NOC and opioid systems, we also discuss overlaps between these systems and present evidence favoring a pharmacological separation between these systems. We finish by outlining the power of the orphan receptor strategy and by discussing some of its pitfalls.
Epratuzumab (Humanized Anti-CD22 MAb) Conjugated with SN-38, a New Antibody-Drug Conjugate (ADC) for the Treatment of Hematologic Tumors: Preclinical Studies Alone and In Combination with Veltuzumab, a Humanized Anti-CD20 MAb (2010)

Abstract Abstract 3941 Background: Monoclonal antibody (MAb) therapy has had a significant impact on the management of B-cell malignancies, but is most often used in combination with chemotherapy. We developed an ADC that combines SN-38, the active component of irinotecan, a topoisomerase I inhibitor, with the internalizing, humanized, anti-CD22 IgG, epratuzumab, and determined its activity alone and in combination with an anti-CD20 antibody therapy (veltuzumab). Methods: Epratuzumab was conjugated with SN-38 (E-SN-38) at a mole ratio of ∼6:1. The conjugate is designed specifically to be released slowly in the presence of serum (50% released over ∼1.5 days), allowing liberation of the drug when internalized, but also being released locally after being bound to the tumor. In vitro and in vivo studies were performed to assess the activity of the conjugate against several subcutaneously- or intravenously-inoculated B-cell lymphoma cell lines. In vivo studies also examined combination therapy using E-SN-38 and the veltuzumab (V). Results: In vitro studies in 4 B-cell lymphoma cells lines (Daudi, Raji, Ramos, WSU-FSCCL) and 4 acute lymphoblastic lymphoma cell lines (697, REH, MN-60, and RS4;11) expressing varying amounts of CD22 showed an IC50 for E-SN-38 in the nanomolar range, confirming potent activity. Nude mice bearing SC Ramos human lymphoma had significant selective anti-tumor activity compared to a control, non-targeting, IgG-SN-38 conjugate, at a dosing regimen of 75 to 250 μg of the conjugates given twice-weekly for 4 weeks. Significant anti-tumor activity was also found in several other cell lines. When combined with veltuzumab, significant improvement in therapeutic activity was observed. For example, median survival in a WSU-FSCCL human follicular B-cell lymphoma IV model with treatment initiated 5 days after implantation was 42 d (0/10 surviving at 160 d) and 91 d (2/10 surviving) for untreated and veltuzumab-treated animals, respectively; 63d (0/10 surviving after 160 d) and &gt;160 d (with 6/10 surviving) for E-SN-38 and E-SN-38 + V, respectively; and 63 d (0/10) and 91 d (2/10) for non-targeting IgG-SN-38 conjugate alone and combined with V). The E-SN-38 conjugate combined with V was significantly better than all treatment or control groups (P ≤ 0.05). Conclusion: E-SN-38 ADC is a potent therapeutic, even at non-toxic dose levels, and shows significantly enhanced efficacy when combined with anti-CD20 immunotherapy, representing an important new ADC treatment regimen. Disclosures: Goldenberg: Immunomedics, Inc.: Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties. Govindan:Immunomedics, Inc.: Employment. Cardillo:Immunomedics, Inc.: Employment.