gebhart/patrepeval huggingface dataset:
Isolation of primitive human bone marrow hematopoietic progenitor cells using Hoechst 33342 and Rhodamine 123. (1996)

In addition to possessing multilineage differentiation and self-renewal capabilities, pluripotent hematopoietic stem cells are believed to be mitotically quiescent and metabolically inactive. Fractions of human bone marrow (BM) CD34+ cells can be further enriched for primitive hematopoietic progenitor cells (HPC) by using a number of cell-surface markers. All of these fractions, however, contain cells that are still heterogeneous as far as their metabolic and mitotic activities are concerned. We therefore used Hoechst 33342 (Hst) to identify quiescent cells and Rhodamine 123 (Rh123) to identify metabolically inactive cells. CD34+HstdimRh123dim (CD34+d/d) and CD34+HstbrightRh123bright (CD34+b/b) cells were isolated by flow cytometry to examine the hematopoietic functions of mitotically and metabolically homogeneous progenitors. Cell-cycle status, progenitor cell content, maintenance of in vitro hematopoiesis, and long-term hematopoietic culture-initiating cell (LTHC-IC) content of CD34+d/d and CD34+b/b cells were compared with CD34+HLA-DR- cells, a well-defined phenotype of primitive HPC. Whereas 99.2 +/- 0.5% of freshly isolated CD34+d/d cells were in G0/G1 phase of the cell cycle, only 74.4 +/- 11.5% of CD34+b/b and 75.6 +/- 1.1% of CD34+HLA-DR- cells were in G0/G1. The number of multipotential progenitors (colony-forming units-granulocyte/erythroid/ macrophage/megakaryocyte [CFU-GEMM]) detected in CD34+d/d cells was twice that observed in CD34+HLA-DR- cells and eight times that in CD34+b/b cells. In stromal cell-free long-term cultures maintained for 10 weeks, production of assayable progenitors in cultures initiated with CD34+d/d cells exceeded that detected in CD34+HLA-DR- cultures by more than three-fold. Only in CD34+d/d cultures were high proliferative potential colony-forming cell (HPP-CFC)-derived colonies detected over a period of 6 weeks. Limiting dilution analysis revealed that the frequency of LTHC-IC was highest among CD34+d/d cells (7.2 +/- 3.3%), followed by a frequency of 4.5 +/- 4.8% for CD34+HLA-DR- cells and 2.2 +/- 3.5% for CD34+b/b cells. The primitive nature of HPC identified by CD34, Hst, and Rh123 was confirmed by the ability of as few as 200 murine marrow cells isolated by this technique to radioprotect and fully reconstitute lethally irradiated recipients. These results indicate that Hst and Rh123 staining can be used in combination with CD34 immunofluorescence to isolate a quiescent subpopulation of human primitive hematopoietic progenitor cells. Cells isolated by this technique appear to have functional properties associated with stem cells, suggesting that they may be ideal candidates for studies requiring primitive HPC, such as ex vivo expansion and somatic gene therapy.
Mining the mutanome: developing highly personalized Immunotherapies based on mutational analysis of tumors (2013)

T cells can mediate remarkable tumor regressions including complete cure in patients with metastatic cancer. Genetic alterations in an individual's cancer cells (the mutanome) encode unique peptides (m-peptides) that can be targets for T cells. The recent advances in next-generation sequencing and computation prediction allows, for the first time, the rapid and affordable identification of m-peptides in individual patients. Despite excitement about the extended spectrum of potential targets in personalized immunotherapy, there is no experience or consensus on the path to their successful clinical application. Major questions remain, such as whether clinical responses to cytokine therapy, T cell transfer, and checkpoint blockade are primarily mediated by m-peptide-specific reactivity, whether m-peptides can be effectively used as vaccines, and which m-peptides are most potently recognized. These and other technological, immunological and translational questions will be explored during a 1-day Workshop on Personalized Cancer Immunotherapy by the Society for Immunotherapy of Cancer, directly before the Annual Meeting, on November 7, 2013 at the National Harbor, MD near Washington, DC.
Improving Diagnosis of Acute Appendicitis: Results of a Diagnostic Pathway with Standard Use of Ultrasonography Followed by Selective Use of CT (2009)

A diagnostic pathway using primary graded compression US and complementary multidetector CT in a general community teaching hospital yields a high diagnostic accuracy for acute appendicitis without adverse events from delay in treatment. Although US is less accurate than CT, it can be used as a primary imaging modality, avoiding the disadvantages of CT. For those patients with negative US and CT findings, observation is safe.
Subcellular localization of Nox4 and regulation in diabetes (2009)

Oxidative stress is implicated in human diseases. Some of the oxidative pathways are harbored in the mitochondria. NAD(P)H oxidases have been identified not only in phagocytic but also in somatic cells. Nox4 is the most ubiquitous of these oxidases and is a major source of reactive oxygen species (ROS) in many cell types and in kidney tissue of diabetic animals. We generated specific Nox4 antibodies, and found that Nox4 localizes to mitochondria. (i) Immunoblot analysis in cultured mesangial cells and kidney cortex revealed that Nox4 is present in crude mitochondria, in mitochondria-enriched heavy fractions, and in purified mitochondria; (ii) immunofluorescence confocal microscopy also revealed that Nox4 localizes with the mitochondrial marker Mitotracker; and (iii) the mitochondrial localization prediction program MitoProt indicated that the probability score for Nox4 is identical to mitochondrial protein cytochrome c oxidase subunit IV. We also show that in purified mitochondria, siRNA-mediated knockdown of Nox4 significantly reduces NADPH oxidase activity in pure mitochondria and blocks glucose-induced mitochondrial superoxide generation. In a rat model of diabetes, mitochondrial Nox4 expression is increased in kidney cortex. Our data provide evidence that a functional Nox4 is present and regulated in mitochondria, indicating the existence of a previously undescribed source of ROS in this organelle.
Post-irradiation aging of ultra-high molecular weight polyethylene. (1994)

A study was performed to determine the time-course of oxidative degradation and the extent to which the degradation proceeded through the bulk of ultra-high molecular weight polyethylene joint components that had been irradiated and stored on a shelf. Standardized cylindrical samples, taken from a single batch of extruded polyethylene, were cleaned, packaged, and sterilized according to protocols used for commercial joint-replacement components. After sterilization, the samples were stored in the packages for time-periods of one day to more than one year. At each interval studied, thin sections were cut as a function of depth into the bulk of the sample and were used to determine the density and the infrared spectra. Marked alterations in the density and the infrared spectra consistent with continuing oxidative degradation occurred throughout the year of storage on the shelf. The alterations were most severe near the surface of the samples.
Secure positioning of wireless devices with application to sensor networks (2005)

So far, the problem of positioning in wireless networks has been mainly studied in a non-adversarial setting. In this work, we analyze the resistance of positioning techniques to position and distance spoofing attacks. We propose a mechanism for secure positioning of wireless devices, that we call verifiable multilateration. We then show how this mechanism can be used to secure positioning in sensor networks. We analyze our system through simulations.
The presence of disseminated tumour cells in the bone marrow is inversely related to circulating free DNA in plasma in breast cancer dormancy (2011)

Our results show that breast cancer patients have evidence of MRD for many years after diagnosis despite there being no overt evidence of disease. The inverse relationship between bone marrow CK19 mRNA and the 291-bp amplicon in cfDNA suggests that an inverse relationship between a measure of cell viability in the bone marrow (DTCs) and cell death in the plasma occurs during the dormancy phase of breast cancer.
Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing (2002)

Antibodies against human leukocyte antigen (HLA) class II, such as 1D10 or Lym-1, are currently being evaluated for the treatment of B-cell lymphomas. Previous studies have demonstrated that, in addition to IgG Fc receptors, the human myeloid IgA receptor (FcαRI, CD89) also effectively triggered tumor cell killing. Therefore, we used the variable light and heavy chain sequences from another murine anti–HLA class II hybridoma, F3.3, to generate a panel of chimeric human/mouse antibodies, including human immunoglobulin A1 (IgA1), IgA2, IgG1, IgG2, IgG3, and IgG4. Antibody production was accomplished by stable transfection of baby hamster kidney cells, and binding activity and specificity were confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. All constructs demonstrated similar binding to HLA class II. Functional studies revealed that chimeric IgG1, IgA1, and IgA2 triggered similar levels of tumor cell lysis. Analyses of effector populations, however, demonstrated that killing by chimeric IgG1 constructs was triggered mainly by human mononuclear cells and complement, while IgA1 and IgA2 mediated effective lysis by polymorphonuclear neutrophils. Importantly, IgG1 and both IgA isotypes were equally effective at killing freshly isolated human chronic lymphocytic leukemia cells. Chimeric IgA antibodies against HLA class II may constitute attractive reagents for lymphoma therapy.
A role in DNA binding for the linker sequences of the first three zinc fingers of TFIIIA (1993)

Zinc fingers of the TFIIIA type are connected by short linker sequences between the structural units. Structural investigations by 2D NMR in solution and by X-ray crystallographic analyses of complexes with DNA point to a passive role for the linkers. We have therefore investigated the influence of the linker sequence on DNA binding using as a model the first three fingers of the protein TFIIIA. Insertion of certain heterologous linkers abolishes binding, and replacement of individual amino acids can reduce binding by factors of up to twenty-four.
Enzymic Synthesis of Lignin Precursors (1976)

A cinnamoyl-coenzyme A reductase catalyzing the NADPH-dependent reduction of substituted cinnamoyl-CoA thiol esters to the corresponding cinnamaldehydes was isolated from cell suspension cultures of soybean (Glycine max L. var. Mandarin). A 1660-fold purification of the enzyme was achieved by (NH4)2SO4 fractionation, chromatography on DEAE-cellulose, hydroxyapatite and Sephadex G-100 and affinity chromatography on 5'-AMP-Sepharose. The apparent molecular weight of the reductase was found to be about 38 000 on the basis of the elution volume from a Sephadex G-100 column. Maximum rate of reaction was observed between pH 6.0 and 6.2 in 0.1-0.2 M citrate buffer at 30 degrees C. The enzyme was markedly inhibited by thiol reagents. The reductase showed a high degree of specificity for cinnamoyl-CoA esters. Feruloyl-CoA was the substrate with the lowest Km value (73 muM) and highest V (230 nkat/mg) followed by 5-hydroxy-feruloyl-CoA, sinapoyl-CoA, p-coumaroyl-CoA, caffeoyl-CoA and cinnamoyl-CoA. No reaction took place with acetyl-CoA. The Km value for NADPH varied with the type of substrate. Km values of 28, 120, and 290 muM were found with feruloyl-CoA, sinapoyl-CoA, and p-coumaroyl-CoA, respectively. The rate of reaction observed with NADH was only about 5% of that found with NADPH. The reaction products CoASH and NADP+ inhibited the reaction. The Ki values were in the range of 0.5-1 mM and the inhibition was of a noncompetitive (mixed) type. The role of the reductase in the biosynthesis of lignin precursors is discussed.
Some factors affecting the performance of a thin film inductance variation magnetometer (1981)

The behaviour of a single domain thin ferromagnetic film used as a sensor element in an inductance variation magnetometer can be predicted. In particular the performance when there is a field component orthogonal to the vector direction of the magnetometer may be evaluated. The effect of uniaxial skew of the film in the bias and sensing fields is also considered. The electronic and magnetic noise of the system are discussed, as they determine the ultimate sensitivity of the device.
Dynamic shaping of orbital-angular-momentum beams for information encoding (2018)

Shaping complex fields with a digital micromirror device (DMD) has attracted much attention recently due to its potential application in optical communication and microscopy. In this paper, we present an optimized Lee method to achieve dynamic shaping of orbital-angular-momentum (OAM) beams using a binary DMD. An error diffusion algorithm is introduced to enhance the accuracy for binary-amplitude hologram design, making it possible to achieve high fidelity wavefront shaping while retaining a high resolution. As a proof of concept, we apply this method to create different classes of OAM beams. The numerical simulations verify that a fidelity of F > 0.985 can be achieved for all the test OAM fields with fully independent phase and amplitude modulation. Moreover, we experimentally demonstrate the dynamic shaping of different OAM beams including pure modes and mixed modes with a switching rate of up to 17.8 kHz. On this basis, accurate information encoding into the generated multiplexed OAM beams is accomplished, which provides access to high speed classical and quantum communications that employ spatial mode encoding.
The Aqueous Humour and the Intraocular Pressure (1990)

The globe of the eye consists essentially of three coats enclosing the transparent refractive media. The outermost, protective tunic is made up of the sclera and cornea—the latter transparent; the middle coat is mainly vascular, consisting of the choroid, ciliary body, and iris. The innermost layer is the retina, containing the essential nervous elements responsible for vision—the rods and cones; it is continued forward over the ciliary body as the ciliary epithelium.
Selective MT 2 melatonin receptor antagonists block melatonin‐mediated phase advances of circadian rhythms (1998)

This study demonstrates the involvement of the MT2 (Mel1b) melatonin receptor in mediating phase advances of circadian activity rhythms by melatonin. In situ hybridization histochemistry with digoxigenin-labeled oligonucleotide probes revealed for the first time the expression of mt1 and MT2 melatonin receptor mRNA within the suprachiasmatic nucleus of the C3H/HeN mouse. Melatonin (0.9 to 30 microg/mouse, s.c.) administration during 3 days at the end of the subjective day (CT 10) to C3H/HeN mice kept in constant dark phase advanced circadian rhythms of wheel running activity in a dose-dependent manner [EC50=0.72 microg/mouse; 0.98+/-0.08 h (n=15) maximal advance at 9 microg/mouse]. Neither the selective MT2 melatonin receptor antagonists 4P-ADOT and 4P-PDOT (90 microg/mouse, s.c.) nor luzindole (300 microg/mouse, s.c.), which shows 25-fold higher affinity for the MT2 than the mt1 subtype, affected the phase of circadian activity rhythms when given alone at CT 10. All three antagonists, however, shifted to the right the dose-response curve to melatonin, as they significantly reduced the phase shifting effects of 0.9 and 3 microg melatonin. This is the first study to demonstrate that melatonin phase advances circadian rhythms by activation of a membrane-bound melatonin receptor and strongly suggests that this effect is mediated through the MT2 melatonin receptor subtype within the circadian timing system. We conclude that the MT2 melatonin receptor subtype is a novel therapeutic target for the development of subtype-selective analogs for the treatment of circadian sleep and mood-related disorders.
Bone Cell Differentiation and Growth Factors (1983)

Bone morphogenetic protein and bone-derived growth factors are biochemical tools for research on induced cell differentiation and local mechanisms controlling cell proliferation. Bone morphogenetic protein irreversibly induces differentiation of perivascular mesenchymal-type cells into osteoprogenitor cells. Bone-derived growth factors are secreted by and for osteoprogenitor cells and stimulate DNA synthesis. Bone generation and regeneration are attributable to the co-efficiency of bone morphogenetic protein and bone-derived growth factors.
Space-code bloom filter for efficient per-flow traffic measurement (2004)

Per-flow traffic measurement is critical for usage accounting, traffic engineering, and anomaly detection. Previous methodologies are either based on random sampling (e.g., Cisco's NetFlow), which is inaccurate, or only account for the "elephants". We introduce a novel technique for measuring per-flow traffic approximately, for all flows regardless of their sizes, at very high-speed (say, OC768). The core of this technique is a novel data structure called space code bloom filter (SCBF). A SCBF is an approximate representation of a multiset; each element in this multiset is a traffic flow and its multiplicity is the number of packets in the flow. The multiplicity of an element in the multiset represented by SCBF can be estimated through either of two mechanisms-maximum likelihood estimation (MLE) or mean value estimation (MVE). Through parameter tuning, SCBF allows for graceful tradeoff between measurement accuracy and computational and storage complexity. SCBF also contributes to the foundation of data streaming by introducing a new paradigm called blind streaming. We evaluate the performance of SCBF through mathematical analysis and through experiments on packet traces gathered from a tier-1 ISP backbone. Our results demonstrate that SCBF achieves reasonable measurement accuracy with very low storage and computational complexity
Trephination of incomplete meniscal tears (1993)

The meniscus performs several roles that are important to the function of the knee joint. In an effort to preserve these functions of the meniscus, methods to promote the healing of meniscal lesions have been investigated. One such method involves trephination or the creation of vascular access channels by removal of a core of tissue from the periphery of the meniscus to the tear, thus connecting a lesion in the avascular portion of the meniscus to the peripheral blood supply. The purpose of this study is to describe our experience with arthroscopic trephination of symptomatic incomplete meniscal tears in humans. This is a simple technique that avoids the risk associated with suture repair of the meniscal tissue, yet preserves the meniscus. Overall results were good or excellent in 90% of the cases. In conclusion, symptomatic incomplete meniscal tears can be treated by stimulation of vascular channels without the risk associated with suturing of this tissue, while preserving the important functions of the meniscus.
Protocells: Modular Mesoporous Silica Nanoparticle‐Supported Lipid Bilayers for Drug Delivery (2016)

Mesoporous silica nanoparticle-supported lipid bilayers, termed 'protocells,' represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single 'magic bullet'. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous silica nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.
Abstract 4761: The iCD40. MyD88 combo-vector: A new platform for enhanced DC tumor immunotherapy (2010)

Abstract Introduction: Given the pre-eminent role of dendritic cells (DCs) as antigen-presenting cells, their exploitation as natural adjuvants in vaccination protocols for the treatment of various malignancies and infectious diseases is not surprising. Nevertheless, inadequate or unsustained activation has likely limited response rates in clinical trials. We previously reported a potent synthetic dimerizer drug-inducible CD40 (iCD40) receptor that permits temporally controlled DC-specific activation within the context of an immunological synapse (Hanks et al, Nat Med, 2005). We showed that when combined with Toll-like Receptor (TLR) adjuvants, iCD40-modified DCs (iCD40-DCs) have enhanced survival, co-stimulatory marker expression, migration, IL-12 production, antigen (Ag)-specific T cell stimulatory capacity and anti-tumor responses (Lapteva et al, Cancer Res, 2007). A phase I/II clinical trial based on iCD40-DCs to treat castration-resistant, metastatic prostate cancer began enrolling patients in August 2009. Procedures: To simplify this approach, we have developed a unified, inducible DC switch, called “iCD40. MyD88”, which combines signaling elements from costimulatory molecule, CD40, and TLR adapter, MyD88, fused to tandem FK506-binding binding proteins (FKBP12v36). Activation is initiated in vitro or in vivo by lipid-permeable dimerizing ligands (i.e. AP1903 or AP20187). Results: Both murine and human iCD40. MyD88-DCs secrete high (ng) levels of IL-12 and maturation markers in a ligand-dependent fashion without the need for exogenous adjuvants. iCD40. MyD88 activation is associated with synergistic activation of IKK&amp;#945;/&amp;#946; and p38. Moreover, tumor-bearing mice treated with antigen-pulsed, iCD40. MyD88-DCs show a potent anti-tumor immune response, consistent with expansion of antigen-specific CTLs in vivo. Bicistronic vectors combining iCD40. MyD88 along with tumor-associated antigens are underway. Conclusion: This “combo-switch” permits potent, targeted activation of antigen-pulsed DCs in vivo, leading to improved anti-tumor immunity with a high likelihood for reduced side effects. Production of a single vector that combines a potent DC switch with tumor antigen is the first requisite step leading to economically viable, “off-the-shelf”, vaccine therapies for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4761.
Inter-Domain Policy Routing Protocol Specification: Version 1 (1993)

This RFC specifies an IAB standards track protocol for the Internet community, and requests discussion