gebhart/patrepeval huggingface dataset:
A serum-free culture model for studying the differentiation of human dendritic cells from adult CD34+ progenitor cells. (1998)

The antigen-presenting capacity of dendritic cells (DCs) makes them attractive potential cellular adjuvants for vaccination strategies. Currently, most in vitro culture systems for the production of these DCs include serum. However, this is undesirable because serum contains growth factors that vary between individuals and could affect DC development. Unless the patient's own serum is used, foreign antigens and the risk of infection will detract from the usefulness of these cells in clinical strategies. In this study we investigated the production of DCs from CD34+ progenitor cells of cancer patients or normal donors under serum-free conditions. We have established a model system for the investigation of DC development and maturation. Dendritic cells that developed from myeloid precursors accumulated after 2 weeks in an intermediate CD1a , CD80-, CD83-, CD86- stage. Intermediate DCs adhered to plastic surfaces, expressed Birbeck granules, and were negative for CD2 and CD14. In the presence of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha, interleukin-4 promoted the development of these stages. Spontaneous maturation of intermediate DCs into fully activated DCs expressing CD83 and costimulatory molecules occurred asynchronously over the ensuing 2 to 3 weeks. This maturation involved increased expression of CD80, CD83, CD86, CMRF-44, HLA-A, -B, -C, and -DR as well as downregulation of CD1a and CD11b. Activated DCs are characterized by the lack of adherence to plastic surfaces and the absence of Birbeck granules. By day 28, these cells were nonphagocytic, potent antigen-presenting cells with an irreversible phenotype. This serum-free system offers advantages in that the process of differentiation and maturation of committed DCs is extended over a period of more than 28 days, allowing investigators to study the effects of individual cytokines or other supplements during distinct phases of DC development in a defined environment.
Reciprocal Relations in Irreversible Processes. II. (1931)

A general reciprocal relation, applicable to transport processes such as the conduction of heat and electricity, and diffusion, is derived from the assumption of microscopic reversibility. In the derivation, certain average products of fluctuations are considered. As a consequence of the general relation $S=k logW$ between entropy and probability, different (coupled) irreversible processes must be compared in terms of entropy changes. If the displacement from thermodynamic equilibrium is described by a set of variables ${\ensuremath{\alpha}}_{1},\ensuremath{\cdots},{\ensuremath{\alpha}}_{n}$, and the relations between the rates ${\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{1},\ensuremath{\cdots},{\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{n}$ and the "forces" $\frac{\ensuremath{\partial}S}{d{\ensuremath{\alpha}}_{1}},\ensuremath{\cdots},\frac{\ensuremath{\partial}S}{d{\ensuremath{\alpha}}_{n}}$ are linear, there exists a quadratic dissipation-function, $2\ensuremath{\Phi}(\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}},\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}})\ensuremath{\equiv}\ensuremath{\Sigma}{\ensuremath{\rho}}_{j}{\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{\mathrm{ij}}{\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{i}=\frac{\mathrm{dS}}{\mathrm{dt}}=\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{S}(\ensuremath{\alpha},\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}})\ensuremath{\equiv}\ensuremath{\Sigma}(\frac{\ensuremath{\partial}S}{d{\ensuremath{\alpha}}_{j}}){\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{j}$ (denoting definition by $\ensuremath{\equiv}$). The symmetry conditions demanded by microscopic reversibility are equivalent to the variation-principle $\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{S}(\ensuremath{\alpha},\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}})\ensuremath{-}\ensuremath{\Phi}(\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}},\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}})=\mathrm{maximum},$ which determines ${\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{1},\ensuremath{\cdots},{\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{\ensuremath{\alpha}}}_{n}$ for prescribed ${\ensuremath{\alpha}}_{1},\ensuremath{\cdots},{\ensuremath{\alpha}}_{n}$. The dissipation-function has a statistical significance similar to that of the entropy. External magnetic fields, and also Coriolis forces, destroy the symmetry in past and future; reciprocal relations involving reversal of the field are formulated.
Tumor-antigen TA-4 in the detection of recurrence in cervical squamous cell carcinoma (1984)

A radioimmunoassay for a tumor-antigen (TA-4) of squamous cell carcinoma was used to detect the recurrence in patients with squamous cell carcinoma of the uterine cervix. Of 17 patients who had recurrence, 15 cases showed reappearance of serum TA-4 levels. Reappearance of serum TA-4 was faster than other clinical signs of recurrence in 11 cases. These results indicated that TA-4 assay would be a useful aid for the detection of recurrence in cervical squamous cell carcinoma.
Analysis of structure and function of the B subunit of cholera toxin by the use of site‐directed mutagenesis (1991)

Oligonucleotide-directed mutagenesis of ctxB was used to produce mutants of cholera toxin B subunit (CT-B) altered at residues Cys-9, Gly-33, Lys-34, Arg-35, Cys-86 and Trp-88. Mutants were identified phenotypically by radial passive immune haemolysis assays and genotypically by colony hybridization with specific oligonucleotide probes. Mutant CT-B polypeptides were characterized for immunoreactivity, binding to ganglioside GM1, ability to associate with the A subunit, ability to form holotoxin, and biological activity. Amino acid substitutions that caused decreased binding of mutant CT-B to ganglioside GM1 and abolished toxicity included negatively charged or large hydrophobic residues for Gly-33 and negatively or positively charged residues for Trp-88. Substitution of lysine or arginine for Gly-33 did not affect immunoreactivity or GM1-binding activity of CT-B but abolished or reduced toxicity of the mutant holotoxins, respectively. Substitutions of Glu or Asp for Arg-35 interfered with formation of holotoxin, but none of the observed substitutions for Lys-34 or Arg-35 affected binding of CT-B to GM1. The Cys-9, Cys-86 and Trp-88 residues were important for establishing or maintaining the native conformation of CT-B or protecting the CT-B polypeptide from rapid degradation in vivo.
Microtechnology (1998)

The Microtechnology thrust area conducts activities for the Lawrence Livermore National Laboratory (LLNL) missions of global security, global ecology, and bioscience. Their efforts are associated with devices, instruments, or systems that require microfabricated components, including micro-electro-mechanical systems (MEMS), electronics, photonics, microstructures, and microactuators. All of their microtechnology work revolves around their microfabrication facility. In all work, they have close collaborations with the various LLNL programs, ensuring that they select those areas for their attention that offer the greatest leverage to LLNL. Their work is driven principally by the applications of their internal programs, and, to a lesser extent, by external applications. For both of these they must have interdisciplinary teams to deliver complete solutions to the problems. The result successes in analytical instrumentation reflect their broad, interdisciplinary base and the cross-fertilization that results from all of the personnel sharing their capabilities and ideas with each other.
Carboxy and Diphosphate Ester Hydrolysis by a Dizinc Complex with a New Alcohol-Pendant Macrocycle (1999)

The synthesis of the new alcohol-pendant macrocycle 4-(2-hydroxyethyl)-1,4,7,16,19,22-hexaaza-10,13,25,28-tetraoxacyclotriacontane (L2) is reported. This ligand contains two different triamine moieties, one of them bearing an ethanolic sidearm. L2 binds two Zn(II) ions in aqueous solution. The stability constants of the L2 complexes have been determined at 298.1 and 308.1 K by means of potentiometric measurements. Besides a [Zn2L2]4+ species, a deprotonated [Zn2(L2-H)]3+ complex and a hydroxo [Zn2(L2-H)(OH)]2+ complex are formed in aqueous solution. Zn(II)-assisted deprotonation of the alcoholic group takes place at neutral pH, giving the [Zn2(L2-H)]3+ complex. In [Zn2(L2-H)]3+, the deprotonated R−O- function bridges the two metals, as shown by the crystal structure of [Zn2(L2-H)Br2]BPh4·MeOH. The hydroxo species [Zn2(L2-H)(OH)]2+ is formed at slightly alkaline pH's. This complex contains both a Zn(II)-bound alkoxide and a Zn(II)−OH nucleophilic function. Therefore, it may provide a simple model system for alkaline phosphatases, where both a deprotonated serine and a Zn−OH function are involved in phosphate ester hydrolysis. Indeed, this complex promotes the hydrolysis of the carboxy ester p-nitrophenyl acetate (NA) as well as the cleavage of phosphate ester bis(p-nitrophenyl) phosphate (BNP). The kinetics of promoted hydrolysis of NA and BNP were studied by means of UV and 1H and 31P NMR measurements. In NA hydrolysis, the R−O-−Zn(II) function acts as nucleophile in the first step of the hydrolytic mechanism, to give an acetyl derivative, which is subsequently hydrolyzed to acetate by a Zn−OH group. Similarly, in BNP cleavage, the nucleophilic attack of alkoxide on phosphorus gives a pendant-alcohol phosphorylated intermediate, which undergoes subsequent intramolecular nucleophilic attack of a Zn(II)-bound hydroxide to yield a phosphomonoester product.
Proteomics: the move to mixtures (2001)

Proteomics can be defined as the systematic analysis of proteins for their identity, quantity and function. In contrast to a cell's static genome, the proteome is both complex and dynamic. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). However, this technique is under scrutiny because of a failure to detect low-abundance proteins from the analysis of whole cell lysates. Alternative approaches integrate a diversity of separation technologies and make use of the tremendous peptide separation and sequencing power provided by MS/MS. When liquid chromatography is combined with tandem mass spectrometry (LC/MS/MS) and applied to the direct analysis of mixtures, many of the limitations of 2DE for proteome analysis can be overcome. This tutorial addresses current approaches to identify and characterize large numbers of proteins and measure dynamic changes in protein expression directly from complex protein mixtures (total cell lysates).
Alveolar macrophage deficiency in osteopetrotic mice deficient in macrophage colony-stimulating factor is spontaneously corrected with age and associated with matrix metalloproteinase expression and emphysema (2001)

Macrophage colony-stimulating factor (M-CSF) is one of several hematologic growth factors capable of regulating the survival, proliferation, and differentiation of macrophages, but its role in modulation of the accumulation and function of alveolar macrophages (AMs) in vivo is not well defined. Osteopetrotic (Op/Op) mice have no detectable M-CSF and show variable tissue-specific reductions in macrophage numbers. It was hypothesized that AMs would be decreased in number and have altered function in Op/Op mice because of the absence of M-CSF. Lung macrophages identified by Mac-3 staining in lung sections were decreased in number in 20-day-old Op/Op mice (P <.001) but not Op/Op mice older than 4 months (P =.68) compared with findings in age-matched littermate controls. The numbers of AMs recovered by bronchoalveolar lavage (BAL) were also reduced in young but not adult Op/Op mice compared with controls. Expression of interleukin-3 (IL-3) was increased in the lungs of Op/Op mice compared with controls as determined by quantification of IL-3 cytokine levels (P =.04), bioactivity (P =.02), and messenger RNA transcript levels. AMs of Op/Op mice spontaneously released higher levels of matrix metalloproteinases (MMPs) than AMs of controls as determined by immunohistochemical staining of AMs and zymographic assessment of BAL fluid and AM lysates. Consistent with an increased release of MMP, Op/Op mice had abnormal elastin deposition and spontaneously developed emphysema in the absence of molecular or cellular evidence of lung inflammation. These data show that the AM deficiency observed in young Op/Op mice is spontaneously corrected with age and is associated with increased lung levels of IL-3, spontaneous MMP expression by AMs, and destruction of lung tissue.
Silicon Photonics: The Next Fabless Semiconductor Industry (2013)

Something very surprising has been happening in photonics recently: the same foundries and processes that were developed to build transistors are being repurposed to build chips that can generate, detect, modulate, and otherwise manipulate light. This is pretty counterintuitive, since the electronics industry spends billions of dollars to develop tools, processes, and facilities that lend themselves to building the very best transistors without any thought about how to make these processes compatible with photonics (with the obvious exception of the processes designed to make CMOS and CCD camera chips).
The role of DNA mismatch repair in drug resistance. (1998)

Loss of DNA mismatch repair (MMR) has been observed in a variety of human cancers. In addition to predisposing to oncogenesis, loss of MMR activity is of concern with respect to the use of chemotherapeutic agents to treat established tumors. Loss of MMR results in drug resistance directly by impairing the ability of the cell to detect DNA damage and activate apoptosis and indirectly by increasing the mutation rate throughout the genome. The MMR proteins are involved in mediating the activation of cell cycle checkpoints and apoptosis in response to DNA damage. MMR-deficient cells have been reported to be resistant to the methylating agents procarbazine and temozolomide, the alkylating agent busulfan, the platinum-containing drugs cisplatin and carboplatin, the antimetabolite 6-thioguanine, and the topoisomerase II inhibitors etoposide and doxorubicin. In the case of cisplatin, busulfan, temozolomide, and procarbazine, the degree of resistance has been shown to be sufficient to produce a large difference in clinical responsiveness in vivo in tumor model systems. The available preclinical data suggest that tumors that contain a significant fraction of cells deficient in MMR will demonstrate reduced responsiveness to specific drugs. The challenge now is to assess the clinical significance of the presence of deficient cells in tumors and to discover drugs that retain activity against MMR-deficient cells.
Unnatural amino acid incorporation in E. coli: current and future applications in the design of therapeutic proteins (2014)

Unnatural amino acid (UAA) incorporation by amber codon suppression offers scientists a powerful tool to modify the properties of proteins at will. UAA incorporation has been used for a plethora of fundamental research applications and, more recently, also for the selective modification of therapeutic proteins. In this review most recent developments in Escherichia coli codon expansion and, unnatural amino acid incorporation are discussed together with some remarkable recent developments in improved efficient UAA incorporation. We focus on the generation of proteins that hold promise for future therapeutic applications that would be impossible to obtain without unnatural amino acid incorporation, including the generation of bi-specific antibodies and antibody drug conjugates.
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells (2012)

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6-secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell-specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6-sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6-producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell-driven pathogenesis in T cell-mediated autoimmune disease such as EAE and MS.
Fabrication of an access coupler with single-strand multimode fiber waveguides (1976)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text M. K. Barnoski and H. R. Friedrich, "Fabrication of an access coupler with single-strand multimode fiber waveguides," Appl. Opt. 15, 2629-2630 (1976) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Nuclear magnetic resonance spectroscopy in diagnostic and investigative medicine. (1984)

N u uclear magnetic resonance (NMR)' spectroscopy, which has been used by chemists and physicists for more than 30 years, is now becoming a powerful technique in the medical sciences because of its unique ability to monitor intracellular metabolites noninvasively.The fundamental principle under- lying NMR spectroscopy is that nuclei of certain atoms, such as hydrogen ('H), phosphorus (31p), carbon (13C), fluorine ('9F), and sodium (23Na), are magnetic dipoles.In the presence of a strong magnetic field, the nuclei of these atoms align with or against the field in much the same way that a bar magnet tends to align itself with the earth's magnetic field.A pulse of perturbing electromagnetic energy at the resonant frequency is then used to tip the nuclei away from their orientation along the magnetic field lines.When the perturbing radiofrequency pulse is stopped, the nuclei return to their original lower energy orientations; in the process, they emit energy which can be picked up by a radiofrequency receiver and transformed, with the aid of a computer, into a spectrum.The different nuclei resonate in the same magnetic field at very different frequencies.For example, at a field of 8.4 T, the 'H-resonance is at 360 MHz while '3C and 3'P are near 90.5 and 145.8 MHz, respectively.Members of the same nuclear species occupying different positions in a molecule resonate at slightly different frequencies.The individual peaks of the spectrum arise from differences in the chemical bondings of individual
Towards the Unification of Navigational Planning and Reactive Control (1989)

The illusion that reactive and hierarchical planning methods are at odds with each other needs to be dropped. By exploiting each method&amp;apos;s strengths, a synthesis of hierarchical and reactive paradigms can yield robust, flexible, and generalizable navigation. Psychological and neuroscientific studies support this claim. 1. Introduction The integration of knowledge-based navigational path planning and reactive navigation requires the confrontation of many difficult problems. It can be seen that each of these methods addresses different subsets of the complexities inherent in intelligent navigation. It is our contention that neither navigational approach is entirely satisfactory when taken in isolation, but rather that both must be taken into account for the production of an intelligent, robust, and flexible system. Navigational path planning without consideration for the difficult issues of plan execution leads to restricted usage in very narrow problem domains and/or extremely brittle m...
Isotype switching by a microinjected mu immunoglobulin heavy chain gene in transgenic mice. (1989)

Immunization of transgenic mice carrying an immunoglobulin mu heavy chain resulted in a response dominated by expression of the transgene variable region. Unexpectedly, in a large proportion of the antibody produced by immunized mice, the transgene variable region was associated with IgG rather than IgM. This demonstrates that the transgene can undergo an isotype switch. Four transgenic founder lines all exhibited transgene isotype switching despite the likelihood of random chromosomal integration of the transgene. In addition one of the lines was analyzed by breeding studies and the transgene was found to be genetically unlinked to the immunoglobulin heavy chain (Igh) locus. These results indicate that a precise chromosomal location is not required for isotype switching and suggest the possibility that the isotype switching process can occur interchromosomally.
Long-period fiber-grating-based gain equalizers (1996)

Long-period fiber gratings are used to f latten the gain spectrum of erbium-doped fiber amplifiers. A broadband amplifier with <0.2-dB gain variation over 30 nm is presented. We also show that a chain of amplifiers can be equalized, leading to a bandwidth enhancement by a factor of 3.
Bacterial Wall as Target for Attack (2003)

When Bacteria, Archaea, and Eucarya separated from each other, a great deal of evolution had taken place. Only then did extensive diversity arise. The bacteria split off with the new property that they had a sacculus that protected them from their own turgor pressure. The saccular wall of murein (or peptidoglycan) was an effective solution to the osmotic pressure problem, but it then was a target for other life-forms, which created lysoymes and beta-lactams. The beta-lactams, with their four-member strained rings, are effective agents in nature and became the first antibiotic in human medicine. But that is by no means the end of the story. Over evolutionary time, bacteria challenged by beta-lactams evolved countermeasures such as beta-lactamases, and the producing organisms evolved variant beta-lactams. The biology of both classes became evident as the pharmaceutical industry isolated, modified, and produced new chemotherapeutic agents and as the properties of beta-lactams and beta-lactamases were examined by molecular techniques. This review attempts to fit the wall biology of current microbes and their clinical context into the way organisms developed on this planet as well as the changes arising since the work done by Fleming. It also outlines the scientific advances in our understanding of this broad area of biology.