gebhart/patrepeval huggingface dataset:
Enzymatically-generated fluorescent detection in micro-channels with internal magnetic mixing for the development of parallel microfluidic ELISA (2006)

The Enzyme-Linked Immuno-Sorbent Assay, or ELISA, is commonly utilized to quantify small concentrations of specific proteins for a large variety of purposes, ranging from medical diagnosis to environmental analysis and food safety. However, this technique requires large volumes of costly reagents and long incubation periods. The use of microfluidics permits one to specifically address these drawbacks by decreasing both the volume and the distance of diffusion inside the micro-channels. Existing microfluidic systems are limited by the necessary control of extremely low flow rates to provide sufficient time for the molecules to interact with each other by diffusion only. In this paper, we describe a new microfluidic design for the realization of parallel ELISA in stop-flow conditions. Magnetic beads were used both as a solid phase to support the formation of the reactive immune complex and to achieve a magnetic mixing inside the channels. In order to test the detection procedure, the formation of the immune complex was performed off-chip before the reactive beads were injected into the reaction chamber. Anti-streptavidin antibodies were quantified with low picomolar sensitivity (0.1-6.7 pM), a linear range of 2 orders of magnitude and good reproducibility. This work represents the first step toward a new platform for simple, highly effective and parallel microfluidic ELISA.
Meniscus-Assisted Magnetic Bead Trapping on Ewod-Based Digital Microfluidics for Specific Protein Localization (2007)

This paper presents a technique to localize specific proteins utilizing magnetic beads (MBs) in digital (droplet) microfluidics, operated by electrowetting-on-dielectric (EWOD). We identify the fundamental differences between digital and continuous microfluidics in utilizing magnetic beads, and demonstrate the technique on an EWOD device. We also show specific, localized concentration of a target protein over antibody-conjugated MBs ("MB-Abs") as proof of concept.
Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy (2005)

The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q(cap)) and muscle O(2) uptake (Vo(2)(m)) in the microcirculation. The purposes of the present study were to estimate the time course of Q(cap) from the kinetics of the primary component of pulmonary O(2) uptake (Vo(2)(p)) and [HHb] throughout exercise, and compare the Q(cap) kinetics with the Vo(2)(p) kinetics. Nine subjects performed moderate- (M; below lactate threshold) and heavy-intensity (H, above lactate threshold) constant-work-rate tests. Vo(2)(p) (l/min) was measured breath by breath, and [HHb] (muM) was measured by NIRS during the tests. The time course of Q(cap) was estimated from the rearrangement of the Fick equation [Q(cap) = Vo(2)(m)/(a-v)O(2), where (a-v)O(2) is arteriovenous O(2) difference] using Vo(2)(p) (primary component) and [HHb] as proxies of Vo(2)(m) and (a-v)O(2), respectively. The kinetics of [HHb] [time constant (tau) + time delay [HHb]; M = 17.8 +/- 2.3 s and H = 13.7 +/- 1.4 s] were significantly (P < 0.001) faster than the kinetics of Vo(2) [tau of primary component (tau(P)); M = 25.5 +/- 8.8 s and H = 25.6 +/- 7.2 s] and Q(cap) [mean response time (MRT); M = 25.4 +/- 9.1 s and H = 25.7 +/- 7.7 s]. However, there was no significant difference between MRT of Q(cap) and tau(P)-Vo(2) for both intensities (P = 0.99), and these parameters were significantly correlated (M and H; r = 0.99; P < 0.001). In conclusion, we have proposed a new method to noninvasively approximate Q(cap) kinetics in humans during exercise. The resulting overall Q(cap) kinetics appeared to be tightly coupled to the temporal profile of Vo(2)(m).
Augmentation of antitumor immunity using genetically M-CSF-expressing L1210 cells. (1996)

Macrophage colony-stimulating factor (M-CSF) enhances tumoricidal activities of macrophages. We transduced human M-CSF cDNA into the mouse lymphoid cell line, L1210, and examined the antitumor effect of the locally expressed M-CSF. Mice injected with the M-CSF-producing subline showed improved survival in comparison with the mock-transfected cell line or parental cell line plus M-CSF administration (20 microg/kg for 3 days) at inoculated cell numbers of 10(2) or 5 x 10(3). The survival rate at 50 days after injection of 10(6) high M-CSF-expressing cells was 80%, significantly higher than that after injection of the mock-transfected cells, which killed all the mice by day 23. The survival rate appeared to depend on the amount of M-CSF produced. Moreover, all surviving mice after intravenous injection of the M-CSF-expressing sublines were rechallenged with 10(6) parental L1210 cells at day 50, and all survived up to day 100, demonstrating that M-CSF-expressing cells induced immune protection against the parental cells. The same improvement of survival was observed in mouse M-CSF-expressing cell lines. These observations imply that M-CSF cDNA is a candidate gene for use in gene therapy in leukemia.
Multifunctional Hydrogels that Promote Osteogenic Human Mesenchymal Stem Cell Differentiation Through Stimulation and Sequestering of Bone Morphogenic Protein 2 (2007)

The extracellular environment controls many cellular activities thereby linking external material cues to internal cell function. By better understanding these processes, synthetic extracellular material niches can be tailored to present cells with highly regulated physical and/or chemical cues that promote or suppress selected cell functions. Here, poly(ethylene glycol) (PEG) hydrogels were functionalized with fluvastatin-releasing grafts and growth factor binding heparin domains to enable the dynamic exchange of information between the material and cells from the outside-in and inside-out (i.e., bidirectional signaling). By incorporating a fluvastatin-releasing graft and carefully controlling the dose and temporal release, materials were designed to promote bone morphogenic protein (BMP2) and alkaline phosphatase (ALP) production by human mesenchymal stem cells (hMSCs). When the release of fluvastatin was controlled to occur over 2 weeks, BMP2 and ALP production was increased 2.2-fold and 1.7-fold, respectively, at day 28 compared to hMSCs cultured in the absence of fluvastatin. By introducing a heparin functionality into the gel to sequester and localize the hMSC-produced BMP2, the osteogenic differentiation of hMSCs was further augmented over fluvastatin delivery alone. Osteopontin and core binding factor α1 gene expression was 6-fold and 4-fold greater for hMSCs exposed to fluvastatin in the presence of the heparin functionalities, respectively. These results demonstrate how multifunctional gels that interact with cells in a bidirectional manner can efficiently promote selected cell functions, such as the osteogenic differentiation of hMSCs.
Restoration of Enzymic Activity by Complementation in Vitro between Mutant α Subunits of Tryptophan Synthetase and between Mutant Subunits and Fragments of the α Subunit (1969)

Abstract The wild type and all mutant α chains of tryptophan synthetase tested can, following denaturation-renaturation, enter into stable dimeric structures. Only certain combinations of mutant α chains yield dimers which have the enzymatic activity which the mutant monomers lack. Most α chains with mutational alterations in the NH2-terminal half of the molecule will complement most α chains that are altered in the COOH-terminal half. One of the five fragments generated by cyanogen bromide cleavage of the α chain complements (restores activity to) an intact mutant α chain. The site of the amino acid change in the mutant subunit is overlapped by the sequence in the fragment. Some fragments of the α chain generated by the presence of a nonsense (ochre) codon in the structural gene for the α chain are able to complement appropriate intact mutant α chains. The relative size of two such fragments is consistent with the map position of the nonsense codons. The presence of large amounts of other Escherichia coli proteins in the urea solution from which α chain dimers are recovered has only a small effect on the ability of α chains to renature as monomers. Similarly, there is little effect of nonspecific protein on the ability of mutant α chains to form functional dimers. In contrast, the β2 subunit of tryptophan synthetase appears to have a specific effect upon both α chain dimer formation and renaturation of the α monomer.
Experimental and theoretical study of a glow discharge at atmospheric pressure controlled by dielectric barrier (1998)

The aim of this paper is to confirm the existence of atmospheric pressure dielectric controlled glow discharge and to describe its main behavior. Electrical measurements, short time exposure photographs, and numerical modeling were used to achieve this task. Experimental observations and numerical simulation are in good agreement. Therefore, the analysis of the calculated space and time variations of the electric field together with the ion and electron densities helps to explain the discharge mechanisms involved, showing the main role played by the electron as well as helium metastable density just before the discharge is turned on.
Antigen- and isotype-specific immune responses to a recombinant antigen-allergen chimeric (RAAC) protein. (1993)

Ag-specific IgE and IgG antibody responses to a recombinant Ag-allergen chimeric (RAAC) protein were examined in B6D2F1 mice. The RAAC protein consisted of the truncated beta-galactosidase (beta-gal), linked at its C terminus to a polypeptide representing the conserved region of the recombinant Kentucky Bluegrass allergen encoded by the cDNA clone KBG8.3(rKBG8.3). Immunization of the mice with the RAAC protein in dextran sulfate as adjuvant led to the differential production of antibodies to the two constituents of RAAC protein with respect to their isotypic classes. Most of the antibody responses to both sets of determinants on the fusion protein were IgG1. In addition, the allergenic polypeptide of RAAC protein induced IgE antibodies, whereas the beta-gal elicited IgG2a antibodies. The same pattern of antibody isotypes was produced when the individual components, rKBG8.3 and beta-gal were separately used for immunization with dextran sulfate. On the other hand, immunization of mice with either RAAC or the beta-gal in CFA induced primarily a IgG response, and no IgE antibodies; however, under the same conditions of immunization rKBG8.3 induced IgG1 antibodies and also low levels of IgE antibodies. In contrast, the RAAC and the beta-gal induced IgG2a antibodies, whereas rKBG8.3 induced no detectable IgG2a antibodies. Furthermore, high titers of IgE antibodies were induced by the rKBG8.3 and not by the RAAC protein in dextran sulfate after the mice had been immunized twice with the same polypeptide in CFA. It is inferred from these results that the induction of isotype-specific immune responses in the animals with the same genetic background is dependent upon the Ag in question as well as the adjuvant; the latter, however, influences the magnitude but does not determine the isotype of the immune responses.
Preventing the Mistraining of Anomaly-Based IDSs through Ensemble Systems (2014)

The security of cloud networks is heavily contingent upon their ability to detect incoming attacks. An Intrusion Detection System (IDS) monitors a network for precisely this purpose. IDSs fall into one of two categories: signature-based and anomaly-based IDSs. Whereas signature-based IDSs rely upon pre-programmed matching rules designed by security experts and are therefore limited to pre-existing attacks in their coverage, anomaly-based IDSs attempt to identify normal and abnormal traffic, generally using machine learning, and therefore hold the promise of being able to identify novel attacks. Anomaly-based IDSs can be divided into IDSs that are trained online and IDSs that are trained offline. While IDSs that are trained online allow greater flexibility, such IDSs could be trained by an adversary to allow specific attacks. This work-in-progress paper proposes a methodology for protecting against the mistraining of an IDS trained online. Two IDSs begin with identical rule sets, but one is allowed to adjust its data to include online data while the other remains static. Both systems can report anomalies, and if the online IDS attempts to let through too much that the offline IDS does not, the decision boundaries of the online IDS are adjusted as a safeguard against mistraining. An experiment for testing the approach is proposed.
[Phenotype alterations of failing myocardium]. (2003)

Compared with the mechanisms of adaptive responses of the heart, the mechanisms of maladaptation have been less elucidated. However, the followings are probably responsible for the progression of heart failure: 1) progressive loss of cardiac myocytes (quantity change); 2) progression of systolic dysfunction of individual myocytes(quality change); or 3) both. Apoptosis may be responsible for the myocyte death although controversial. Myocytes of failing hearts shows dramatic phenotype alterations in the structure, function, and biochemical events such as fetal type gene induction. Hypertrophy and degeneration of myocytes are the common, but not specific, features in failing hearts. Meanwhile, not only myocyte phenotype alterations but also myocardial interstitial changes such as extracellular matrix deposition, activation of fibroblasts, and narrowing of vessel lumens play important roles for the progression of heart failure.
Age-Dependent Disease Expression Determines Remodeling of the Retinal Mosaic in Carriers ofRPGRExon ORF15 Mutations (2009)

The time of onset and the progression of the disease differed between the two models. In the early-onset form (XLPRA2) the morphologic appearance of the retinal mosaic changed as a function of age, suggesting that structural plasticity persists in the early postnatal canine retina as mutant photoreceptors die. In the late-onset form (XLPRA1), patches of disease persisted until later ages.
Regulation of base excision repair: Ntg1 nuclear and mitochondrial dynamic localization in response to genotoxic stress (2010)

Numerous human pathologies result from unrepaired oxidative DNA damage. Base excision repair (BER) is responsible for the repair of oxidative DNA damage that occurs in both nuclei and mitochondria. Despite the importance of BER in maintaining genomic stability, knowledge concerning the regulation of this evolutionarily conserved repair pathway is almost nonexistent. The Saccharomyces cerevisiae BER protein, Ntg1, relocalizes to organelles containing elevated oxidative DNA damage, indicating a novel mechanism of regulation for BER. We propose that dynamic localization of BER proteins is modulated by constituents of stress response pathways. In an effort to mechanistically define these regulatory components, the elements necessary for nuclear and mitochondrial localization of Ntg1 were identified, including a bipartite classical nuclear localization signal, a mitochondrial matrix targeting sequence and the classical nuclear protein import machinery. Our results define a major regulatory system for BER which when compromised, confers a mutator phenotype and sensitizes cells to the cytotoxic effects of DNA damage.
Th17 Cell-Mediated Neuroinflammation Is Involved in Neurodegeneration of Aβ1-42-Induced Alzheimer’s Disease Model Rats (2013)

Neuroinflammation, especially innate immunocyte-mediated neuroinflammation, has been reported to participate in pathogenesis of Alzheimer's disease (AD). However, the involvement of adaptive immune cells, such as CD4(+) T lymphocytes, in pathogenesis of AD is not well clarified. Herein, we focus on T helper 17 (Th17) cells, a subpopulation of CD4(+) T cells with high proinflammation, and show the implication of the cells in neurodegeneration of AD. Amyloid β1-42 (Aβ1-42) was bilaterally injected into hippocampus of rats to induce AD. On days 7 and 14 following the Aβ1-42 administration, escape latency of the rats in Morris water maze was increased, expression of amyloid precursor protein was upregulated, but expression of protein phosphatase 2A was downregulated in the hippocampus, and Nissl stain showed neuronal loss and gliosis in CA1 region. Infusion of FITC-linked albumin in blood circulation and combination with immunostaining of hippocampal sections for RORγ, a specific transcriptional factor of Th17 cells, demonstrated blood-brain barrier (BBB) disruption and Th17 cells' infiltration into brain parenchyma of AD rats. Expression of Th17 proinflammatory cytokines, interleukin (IL)-17 and IL-22, was increased in the hippocampus, and concentrations of the two cytokines were elevated in both the cerebrospinal fluid and the serum in AD occurrence and development. Compared with intact or saline-treated control rats, AD animals indicated an upregulated expression of Fas and FasL in the hippocampus. Further, the immunofluorescent histochemistry on AD hippocampal sections with NeuN, RORγ, Fas and FasL displayed that Fas was principally expressed by neurons and FasL was predominantly expressed by Th17 cells, and that neuronal apoptosis shown by TUNEL and NeuN double-labeled cells increased. These results suggest that Th17 cells, which were infiltrated into AD brain parenchyma, participate in neuroinflammation and neurodegeneration of AD by release of proinflammatory cytokines and by direct action on neurons via Fas/FasL apoptotic pathway.
Identification of HLA‐A24 epitope peptides of carcinoembryonic antigen which induce tumor‐reactive cytotoxic T lymphocyte (1999)

Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. HLA-A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8+ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide-pulsed dendritic cells as antigen-presenting cells. This approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and CEA. The cytotoxicity to tumor cells by the CTL lines was antigen-specific since it was inhibited by peptide-pulsed cold target cells as well as by anti-class I major histocompatibility complex (MHC) and anti-CD3 monoclonal antibodies (MAbs). The antigen specificity of the 2 CTL lines was examined using several tumor cell lines of various origins and for their peptide-dose responses. The identification of these novel CEA epitopes for CTL offers the opportunity to design and develop epitope-based immunotherapeutic approaches for treating HLA-A24+ patients with tumors that express CEA. Int. J. Cancer 80:92–97, 1999. © 1999 Wiley-Liss, Inc.
Es ilegal la deuda externa ante el derecho internacional (1989)

Es posible alegar la nulidad de la deuda externa en base a solidos fundamentos del derecho internacional: aplicacion de la clausula rebus sic stantibus, teoria del riesgo creado, imposibilidad de cumplimiento, doctrina de las deudas odiosas, enriquecimiento ilicito, que constituyen principios fundamentales de nuestros sistemas juridicos. Ademas, la deuda externa afecta a los derechos humanos, que constituyen normas obligatorias (ius cogens) del derecho internacional, en cuanto a nivel de vida, soberania politica y economica, y autodeterminacion. Se debe ir a la aprobacion de un Codigo de Conducta sobre la deuda externa y cautelar, asimismo, el derecho al desarrollo de nuestros paises, asi como aumentar el control local sobre las transnacionales.
NMR body images (1976)

It was interesting to read in the January issue of Physics Bulletin (page 15) that the Medical Research Council has committed itself to supporting research into the development of techniques for wholebody imaging based on NMR. The National Research Development Corporation has for some time been supporting several workers in this field by filing patent applications on their behalf.
New Strategies in Estrogen Receptor–Positive Breast Cancer (2010)

Endocrine therapy has led to a significant improvement in outcomes for women with estrogen receptor-positive (ER+) breast cancer. Current questions in the adjuvant setting include the optimal duration of endocrine therapy, and the accurate molecular prediction of endocrine responsiveness using gene array-based assays compared with ER expression itself. In advanced disease, novel selective estrogen receptor antagonists (SERM) have failed to make an impact, although the pure ER antagonist fulvestrant may have a role, albeit optimal dose and sequence remain unclear. Overcoming de novo or acquired endocrine resistance remains critical to enhancing further the benefit of existing endocrine therapies. Recent progress has been made in understanding the molecular biology associated with acquired endocrine resistance, including adaptive "cross-talk" between ER and peptide growth factor receptor pathways such as epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2). Future strategies that are being evaluated include combining endocrine therapy with inhibitors of growth factor receptors or downstream signaling pathways, to treat or prevent critical resistance pathways that become operative in ER+ tumors. Preclinical experiments have provided great promise for this approach, although clinical data remain mixed. Enriching trial recruitment by molecular profiling of different ER+ subtypes will become increasingly important to maximize additional benefit that new agents may bring to current endocrine therapies for breast cancer.
New Strategies to Establish Human Monoclonal Antibodies. (1992)

In order to establish human monoclonal antibodies to any sort of antigens efficiently, we have made following two approaches. Our first approach is to improve cell fusion frequency. By improving our previous method for production of human hybridomas, we obtained higher frequency (1/700 vs. 1/5500) compared with our previous method by adding irradiated myeloma cells to culture of fusion cells and modifying the selective medium. Our second approach is to use a SCID-hu mouse for immunization. Since the injection of human PBL can result in the stable long-term reconstitution of a human immune system in SCID mouse, we tried to immune SCID-hu mouse with KLH. In the serum of immunized SCID-hu mouse, we obtained human IgG antibodies to KLH. Additionally, we succeeded in establishing human B lymphoblastoid cell lines which produced antibodies specific to KLH. These methods will open new prospects for the detection and therapy of cancer.
Noninvasive prenatal diagnosis empowered by high‐throughput sequencing (2012)

A number of multicenter studies have since been conducted to evaluate the diagnostic efficacy of the sequencing-based method. To date, the literature contains results for the analysis of a total of 305 trisomy 21 pregnancies and 2061 euploid pregnancies. The overall diagnostic sensitivity and specificity were both 99%. Besides trisomy 21, massively parallel maternal plasma DNA sequencing has also been applied to the noninvasive detection of trisomy 18, trisomy 13 and fetal genetic sequences across the genome.
Accuracy of Ultrasound for the Diagnosis of Deep Venous Thrombosis in Asymptomatic Patients after Orthopedic Surgery (1995)

Venous ultrasound imaging has only moderate sensitivity and a moderate positive predictive value when used to screen for deep venous thrombosis in patients after orthopedic surgery; thus, ultrasound imaging may have limitations as a screening test.