gebhart/patrepeval huggingface dataset:
Neuroactive steroids for the treatment of status epilepticus (2013)

Benzodiazepines are the current first-line standard-of-care treatment for status epilepticus but fail to terminate seizures in about one third of cases. Synaptic GABAA receptors, which mediate phasic inhibition in central circuits, are the molecular target of benzodiazepines. As status epilepticus progresses, these receptors are internalized and become functionally inactivated, conferring benzodiazepine resistance, which is believed to be a major cause of treatment failure. GABAA receptor positive allosteric modulator neuroactive steroids, such as allopregnanolone, also potentiate synaptic GABAA receptors, but in addition they enhance extrasynaptic GABAA receptors that mediate tonic inhibition. Extrasynaptic GABAA receptors are not internalized, and desensitization of these receptors does not occur during continuous seizures in status epilepticus models. Here we review the broad-spectrum antiseizure activity of allopregnanolone in animal seizure models and the evidence for its activity in models of status epilepticus. We also demonstrate that allopregnanolone inhibits ongoing behavioral and electrographic seizures in a model of status epilepticus, even when there is benzodiazepine resistance. Parenteral allopregnanolone may provide an improved treatment for refractory status epilepticus.
Photonic transport network architecture and OA&M technologies to create large-scale robust networks (1998)

In order to realize a large-scale and robust photonic transport network, a network protection strategy and operation, administration, and management (OA&M) realization scheme in wavelength division multiplexing optical path (WDM OP) transport networks has been developed. This paper discusses the networking (restoration/protection) concepts in each optical layer and proposes the most suitable networking strategy. To develop the OA&M technique, the characteristic information format of each optical layer must be discerned. A network node interface (NNI) structure for the WDM OP transport network is proposed. The proposed NNI is defined as the optical transport module (OTM). An OP signal format is defined as the optical transport unit (OTU). Overhead information and schemes to transmit it are also discussed.
Analytical Validation of the Oncotype DX Genomic Diagnostic Test for Recurrence Prognosis and Therapeutic Response Prediction in Node-Negative, Estrogen Receptor–Positive Breast Cancer (2007)

The analytical and operational performance specifications defined for the Oncotype DX assay allow the reporting of quantitative RS values for individual patients with an SD within 2 RS units on a 100-unit scale.
Haemostasis in Fish – An Evolutionary Perspective (1997)

The original studies referred to in this review were partially supported by the Wellcome Trust (042316/Z/94/Z). D. J. H. was supported by a studentship from the Biotechnology and Biological Sciences Research Council, UK.
Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes (2002)

ABSTRACT Although Nef has been proposed to effect the escape of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTL) through downmodulation of major histocompatibility complex class I molecules, little direct data have been presented previously to support this hypothesis. By comparing nef -competent and nef -deleted HIV-1 strains in an in vitro coculture system, we demonstrate that the presence of this viral accessory gene leads to impairment of the ability of HIV-1-specific CTL clones to suppress viral replication. Furthermore, inhibition by genetically modified CTL that do not require major histocompatibility complex class I-presented antigen (expressing the CD4 T-cell receptor [TCR] ζ-chain hybrid receptor) is similar for both nef -competent and -deleted strains, indicating that Nef does not impair the effector functions of CTL but acts at the level of TCR triggering. In contrast, we note that another accessory gene, vpr , does not induce resistance of HIV-1 to suppression by CTL clones. We conclude that Nef (and not Vpr) contributes to functional HIV-1 immune evasion and that this effect is mediated by diminished antigen presentation to CTL.
Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily. (1992)

We have cloned the human homolog of the v-mpl oncogene transduced in the myeloproliferative leukemia retrovirus, which presents striking homologies with members of the hematopoietin receptor superfamily. We obtained two types of clones, MPLP and MPLK, which had the same 5' extremity but differed at their 3' ends. The resulting deduced polypeptides are composed of a common extracellular domain with a putative signal sequence and a common transmembrane domain, but they differ in their cytoplasmic domain after a stretch of 9 common amino acids. The extracellular domain of MPL contains the consensus sequences described for the members of the hematopoietin receptor superfamily. In addition, as for murine interleukin 3 and human and murine granulocyte-macrophage colony-stimulating factor type beta receptors, this domain can be divided into two subunits. An additional motif specific for MPL could be displayed by hydrophobic cluster analysis in the first subdomain. When RNAs from various hematopoietic cell lines were analyzed by Northern blot, MPL was detected only in the human erythroleukemia (HEL) cell line as a major 3.7-kilobase (kb) mRNA (MPLP) and a minor 2.8-kb mRNA (MPLK). However, study of MPL expression by PCR analysis indicated that MPL is expressed at a low level in a large number of cells of hematopoietic origin and that the two types of mRNAs (P and K) were always found to be coexpressed.
Modulation of the Specificity and Activity of a Cellular Promoter in an Adenoviral Vector (1997)

Most gene therapy studies with recombinant adenoviruses employ viral promoters and lack tissue specificity. To determine whether a tissue-specific cellular promoter inserted into the adenoviral genome can direct the expression of a reporter gene in a tissue-specific manner, recombinant adenoviruses containing a nuclear lacZ gene driven by a human ventricular/slow muscle myosin light chain 1 promoter with and without a muscle creatine kinase enhancer were constructed. The ability of these viruses to express the reporter genes in infected myogenic and nonmyogenic cell lines was studied. Intramuscular injection of these viruses into mice showed that little or no reporter gene expression occurred in muscle fibers, although a relatively high level of lacZ gene expression was observed in surrounding connective tissue. Insertion of adenovirus sequences from the 5' inverted terminal repeat (ITR) region and/or the protein IX region into plasmids resulted in decreased reporter gene expression from myosin light chain 1 promoter in transfected C2C12 myotubes and 293 cells, as well as in injected muscles. These results suggested that negative elements are present in the adenoviral genome. This negative effect seems neither tissue nor species specific. Adenovirus cis-elements that may affect the specificity and activity of a cellular promoter are discussed.
Epididymal protein Rnase10 is required for post‐testicular sperm maturation and male fertility (2012)

Eutherian spermatozoa are dependent on the environment of the proximal epididymis to complete their maturation; however, no specific epididymal factors that mediate this process have so far been identified. Here, we show that targeted disruption of the novel gene Rnase10 encoding a secreted proximal epididymal protein in the mouse results in a binding defect in spermatozoa and their inability to pass through the uterotubal junction in the female. The failure to gain the site of fertilization in the knockout spermatozoa is associated with a gradual loss of ADAM3 and ADAM6 proteins during epididymal transit. In the distal epididymis, these spermatozoa appear to lack calcium-dependent associations with the immobilizing glutinous extracellular material and are released as single, vigorously motile cells that display no tendency for head-to-head agglutination and lack affinity to the oviductal epithelium. In sperm-egg binding assay, they are unable to establish a tenacious association with the zona pellucida, yet they are capable of fertilization. Furthermore, these sperm show accelerated capacitation resulting in an overall in vitro fertilizing ability superior to that of wild-type sperm. We conclude that the physiological role of sperm adhesiveness is in the mechanism of restricted sperm entry into the oviduct rather than in sperm-egg interaction.
High Resolution Radar Imaging (1988)

Abstract : The goal of this project is to formulate and investigate new approaches for forming images of radar targets from spotlight-mode, delay- doppler measurements. These measurements could be acquired with a high- resolution radar-imaging system operating with an optical- or radio-frequency carrier. Two approaches are under study. The first is motivated by an image- reconstruction method used in radionuclide imaging called the confidence- weighted algorithm; here, we refer to this approach as the chirp-rate modulation approach. The second approach is based on more fundamental principles which starts with a mathematical model that accurately describes the physics of an imaging radar-system and then uses statistical-estimation theory with this model to derive methods for producing target images; we refer to this as the estimation-theory approach.
Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells (2005)

Interactions between B and T cells are essential for most antibody responses, but the dynamics of these interactions are poorly understood. By two-photon microscopy of intact lymph nodes, we show that upon exposure to antigen, B cells migrate with directional preference toward the B-zone-T-zone boundary in a CCR7-dependent manner, through a region that exhibits a CCR7-ligand gradient. Initially the B cells show reduced motility, but after 1 d, motility is increased to approximately 9 microm/min. Antigen-engaged B cells pair with antigen-specific helper T cells for 10 to more than 60 min, whereas non-antigen-specific interactions last less than 10 min. B cell-T cell conjugates are highly dynamic and migrate extensively, being led by B cells. B cells occasionally contact more than one T cell, whereas T cells are strictly monogamous in their interactions. These findings provide evidence of lymphocyte chemotaxis in vivo, and they begin to define the spatiotemporal cellular dynamics associated with T cell-dependent antibody responses.
A Computational Architecture for Programmable Automation Research (1987)

This short paper describes recent work at the IBM T. J. Watson Research Center directed at developing a highly flexible computational architecture for research on sensor-based programmable automation. The system described here has been designed with a focus on dynamic configurability, layered user inter-faces and incorporation of sensor-based real time operations into new commands. It is these features which distinguish it from earlier work. The system is cur-rently being implemented at IBM for research purposes and internal use and is an outgrowth of programmable automation research which has been ongoing since 1972 [e.g., 1, 2, 3, 4, 5, 6] .
The expression of mouse gene P1A in testis does not prevent safe induction of cytolytic T cells against a P1A‐encoded tumor antigen (1997)

Tumor antigen P815AB is recognized by cytolytic T lymphocytes (CTL) on mouse mastocytoma P815. This antigen is encoded by P1A, a gene activated in several tumors but silent in normal tissues except for testis and placenta. Notwithstanding the expression of P1A in testis, we found that male mice mounted P815AB-specific CTL responses as efficiently as females. The responding males remained fertile and no autoimmune lesions were observed in their testes. By immunohistochemistry with a rabbit antiserum directed against the P1A protein, we identified spermatogonia as the testicular cells expressing P1A. The absence of MHC class-1 molecules on spermatogonia could be one of the mechanisms of protection against testicular autoimmunity, as the antigenic peptide should not be displayed at the cell surface. Human genes MAGE, BAGE and GAGE, which also code for tumor antigens recognized by autologous CTL, are not expressed in normal tissues other than testis. The results obtained in mice with antigen P815AB suggest that immunization of human males with such antigens will not generate autoimmune side-effects. Although P1A is strongly expressed in placenta, we also found that gestation did not prevent generation of CTL responses against antigen P815AB, and that such CTL responses did not affect gestation outcome. We identified labyrinthine trophoblasts as the placental cells expressing P1A. Again, the absence of MHC class-1 molecules on these cells provides a plausible explanation for placental protection, although other mechanisms may also play a role. Int. J. Cancer, 70:349–356, 1997. © 1997 Wiley-Liss, Inc.
Assignment of genes for human monoamine oxidases A and B to the X chromosome (1986)

Monoclonal antibodies that immunoprecipitate human monoamine oxidase (MAO) A or human MAO B, but not the corresponding mouse enzymes, were used to assay for the presence of immunoprecipitable MAO A or MAO B (presumably coded by the respective human genes) in mouse-human hybrid somatic cell lines containing small numbers of human chromosomes. The results were as follow: Extracts of a human lymphoblastoid x mouse hepatoma hybrid line that retained the human X chromosome contained immunoprecipitable MAO B, while a similar hybrid line that contained the same human chromosomes, except for the human X, did not. Extracts of a human fibroblast x mouse neuroblastoma hybrid cell line, whose human chromosomal material consisted solely of the X, contained both immunoprecipitable MAO A and MAO B. Extracts of a related hybrid line, whose human chromosomal material consisted solely of an autonomous fragment and a fragment translocated to a mouse chromosome, contained immunoprecipitable MAO A. However, the level of immunoprecipitable MAO B activity in extracts of this hybrid was low or undetectable. Among extracts of 33 human fibroblast x mouse hepatoma hybrids that had been selected for expression of the X-linked human enzyme HPRT, 60% contained immunoprecipitable MAO B. This figure was comparable to the 58% that expressed the X-linked human isozyme for glucose-6-phosphate dehydrogenase (G6PD). When 11 of these hybrid lines, which contained immunoprecipitable MAO B and human HPRT, were selected for loss of HPRT, all lost immunoprecipitable MAO B in addition to HPRT. These data demonstrate that genes controlling the expression of MAO A and MAO B, which can be immunoprecipitated with the human-specific monoclonal antibodies, are located on the human X chromosome. Properties of the immunological epitopes recognized by the monoclonal antibodies suggest that the X-linked genes detected in this study are probably structural genes for the enzymes.
Anatomy of protein structures: Visualizing how a one-dimensional protein chain folds into a three-dimensional shape (2000)

Here, we depict the anatomy of protein structures in terms of the protein folding process. Via an iterative, top-down dissecting procedure, tertiary structures are spliced down to reveal their anatomy: first, to produce domains (defined by visual three-dimensional inspection criteria); then, hydrophobic folding units (HFU); and, at the end of a multilevel process, a set of building blocks. The resulting anatomy tree organization not only clearly depicts the organization of a one-dimensional polypeptide chain in three-dimensional space but also straightforwardly describes the most likely folding pathway(s). Comparison of the tree with the formation of the hydrophobic folding units through combinatorial assembly of the building blocks illustrates how the chain folds in a sequential or a complex folding pathway. Further, the tree points to the kinetics of the folding, whether the chain is a fast or a slow folder, and the probability of misfolding. Our ability to successfully dissect the protein into an anatomy tree illustrates that protein folding is a hierarchical process and further validates a building blocks protein folding model.
Inactivation of factor Va by plasmin. (1987)

The inactivation of Factor Va by plasmin was studied in the presence and absence of phospholipid vesicles and calcium ions. The cleavage patterns of bovine Factor Va and its isolated subunits were analyzed using polyacrylamide gel electrophoresis, and the progress of inactivation was monitored by clotting assays and measurements of prothrombin activation using 5-dimethylaminonaphthalene-1-sulfonylarginine-N-(3-ethyl-1,5-penta nediyl)amide. In addition, the ability of prothrombin and Factor Xa to protect Factor Va from inactivation by human plasmin was examined. The data presented indicate that the cofactor Factor Va is inactivated rapidly upon its interaction with human plasmin. The rate of inactivation is significantly enhanced in the presence of phospholipid vesicles, suggesting that the inactivation process is a membrane-bound phenomenon. The isolated D component (heavy chain of factor Va) was found to be slowly degraded by human plasmin, giving rise to cleavage products different from those obtained with activated protein C and Factor Xa. However, the 48- and 30-kDa fragments obtained from human plasmin degradation of component E (light chain of Factor Va) appear to be similar to those obtained following the proteolysis of the same subunit by activated protein C and Factor Xa.
Whole-body three-dimensional optoacoustic tomography system for small animals (2009)

We develop a system for three-dimensional whole-body optoacoustic tomography of small animals for applications in preclinical research. The tomographic images are obtained while the objects of study (phantoms or mice) are rotated within a sphere outlined by a concave arc-shaped array of 64 piezocomposite transducers. Two pulsed lasers operating in the near-IR spectral range (755 and 1064 nm) with an average pulsed energy of about 100 mJ, a repetition rate of 10 Hz, and a pulse duration of 15 to 75 ns are used as optical illumination sources. During the scan, the mouse is illuminated orthogonally to the array with two wide beams of light from a bifurcated fiber bundle. The system is capable of generating images of individual organs and blood vessels through the entire body of a mouse with spatial resolution of approximately 0.5 mm.
Impact of Acute Biventricular Pacing on Left Ventricular Performance and Volumes in Patients with Severe Heart Failure (2001)

Biventricular pacing improves LV systolic performance and reduces LV volumes during short-term treatment. TVI provides important pathophysiological information on the degree of LV resynchronization and may contribute to improved patient selection.
A rapid and sensitive assay for histone acetyl-transferase activity (1998)

Histone acetyl-transferases (HATs) seem to be key elements in the regulation of transcription. We have designed an enzymatic assay to quantify HAT enzymatic activity. In this assay, the substrate is a peptide corresponding to the 24 first amino acids of histone H4 which is coupled to biotin. After acetylation using [14C]acetyl-CoA, the peptide is purified on streptavidin beads and the associated radioactivity is measured. This assay is sensitive, rapid and convenient.
Vibration Signal Transmission in Spider Orb Webs (1981)

Vibration transmission from the prey-catching region to the hub of the unloaded orb web of Nuctenea sclopetaria was measured by laser vibrometry. Compared to transverse or lateral vibrations, longitudinal vibration shows less attenuation and contains more directional information. It is transmitted well throughout the entire frequency range measured (1 to 10,000 hertz).
Occurrence and Control of Soybean Aphid, Aphis glycines Matsumura (2017)

The soybean aphid, Aphis glycines Matsumura, is one of the most important pests of soybean. The A. glycines outbreak in 1998 followed another aphid outbreak after 1989, which caused enormous economic losses. The aphid infested areas exceeded 200 thousand mu, and the soybean yields decreased by 20%. Among aphid infested areas, 78 thousand mu were severely infested with a yield loss of 46%. More than 3,000 mu had no yield at all.
The induction of in vivo proliferation of long-lived CD44hi CD8+ T cells after the injection of tumor cells expressing IFN-alpha1 into syngeneic mice. (1998)

The tumorigenicity of transplantable tumor cells in mice is reduced by transduction with cytokine genes, including IFN-alpha and interleukin (IL) 12. Although T cells are considered important in tumor rejection, the mechanism by which genetically modified tumor cells stimulate the immune system has not been examined. In this study, the in vivo proliferation of T-cell subsets in mice transplanted with cytokine-producing syngeneic tumor cells was assessed by administering the DNA precursor bromodeoxyuridine. The injection of viable cells producing IFN-alpha or IL-12 caused a marked proliferation of CD8+ T lymphocytes in both the spleen and lymph nodes. Proliferation was most prominent among memory-phenotype CD44hi CD8+ T cells. In contrast, proliferation of CD8+ T cells did not occur in mice injected with control cells or with cells expressing IL-4, granulocyte colony-stimulating factor, or IFN-gamma. Pulse-chase studies in mice injected with IFN-alpha-producing cells showed that a proportion of proliferating CD8+ T cells survived for at least 70 days, suggesting that long-lived memory cells are induced using such an approach. In summary, these results, together with previous studies on the host immune reactivity triggered by the injection of tumor cells expressing IFN-alpha, represent a strong rationale for considering IFN-alpha as a powerful T-cell adjuvant for the generation of more effective cancer vaccines.
Hepatic Gene Transfer as a Means of Tolerance Induction to Transgene Products (2009)

The liver is a preferred target organ for gene therapy not only for liver-specific diseases but also for disorders that require systemic delivery of a protein. Diseases that could benefit from hepatic gene transfer include hemophilia, metabolic disorders, lysosomal storage disorders, and others. For a successful delivery of the transgene and sustained expression, the protocol must avoid immune responses in order to be efficacious. A growing number of studies have demonstrated that liver-directed transfer can induce transgene product-specific immune tolerance. Tolerance obtained via this route requires optimal engineering of the vector to eliminate transgene expression in antigen presenting cells while restricting high levels of therapeutic expression to hepatocytes. Innate immune responses may prevent tolerance induction, cause toxicity, and have to be minimized. Discussed in our review is the crucial role of CD4(+)CD25(+) regulatory T cells in tolerance to the hepatocyte-derived gene product, the immunobiology of the liver and our current understanding of its tolerogenic properties, current and proposed research as to the mechanisms behind the liver's unique cellular environment, as well as development of the tools for tolerance induction such as advanced vector systems.