gebhart/patrepeval huggingface dataset:
Hierarchical Modeling for Rare Event Detection and Cell Subset Alignment across Flow Cytometry Samples (2013)

Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less). Standard analysis of flow cytometry data relies on visual identification of cell subsets by experts, a process that is subjective and often difficult to reproduce. An alternative and more objective approach is the use of statistical models to identify cell subsets of interest in an automated fashion. Two specific challenges for automated analysis are to detect extremely low frequency event subsets without biasing the estimate by pre-processing enrichment, and the ability to align cell subsets across multiple data samples for comparative analysis. In this manuscript, we develop hierarchical modeling extensions to the Dirichlet Process Gaussian Mixture Model (DPGMM) approach we have previously described for cell subset identification, and show that the hierarchical DPGMM (HDPGMM) naturally generates an aligned data model that captures both commonalities and variations across multiple samples. HDPGMM also increases the sensitivity to extremely low frequency events by sharing information across multiple samples analyzed simultaneously. We validate the accuracy and reproducibility of HDPGMM estimates of antigen-specific T cells on clinically relevant reference peripheral blood mononuclear cell (PBMC) samples with known frequencies of antigen-specific T cells. These cell samples take advantage of retrovirally TCR-transduced T cells spiked into autologous PBMC samples to give a defined number of antigen-specific T cells detectable by HLA-peptide multimer binding. We provide open source software that can take advantage of both multiple processors and GPU-acceleration to perform the numerically-demanding computations. We show that hierarchical modeling is a useful probabilistic approach that can provide a consistent labeling of cell subsets and increase the sensitivity of rare event detection in the context of quantifying antigen-specific immune responses.
Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus<sup>1</sup> (2007)

Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pretreatment with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain.
Lewis Acid-Catalyzed Cyclization of Enaminones with Propargylic Alcohols: Regioselective Synthesis of Multisubstituted 1,2-Dihydropyridines (2013)

A highly efficient BF3·Et2O-catalyzed cascade reaction of enaminones with propargylic alcohols under mild reaction conditions has been developed. This methodology offers regioselective access to multisubstituted 1,2-dihydropyridines in good to excellent yields.
Thermotropic characterization of phosphatidylcholine vesicles containing ganglioside Gm1 with homogeneous ceramide chain length (1986)

The thermotropic behavior of dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine large unilamellar vesicles containing ganglioside GM1 of homogeneous long chain base composition has been studied by high-sensitivity differential scanning calorimetry and fluorescence spectroscopy. At neutral pH and in the absence of Ca2+, the thermotropic behavior of these systems is independent of the ganglioside chain length composition. The presence of Ca2+ at concentrations higher than 5 mM induces ganglioside phase separation in a manner dependent upon the length difference between the ganglioside long chain base and the phosphatidylcholine acyl chains. The analysis of the chain length dependence of the thermotropic behavior suggests that the driving force for ganglioside phase separation is not a Ca2+-induced cross-bridging of the ganglioside head group but a passive ganglioside exclusion from Ca2+-perturbed phosphatidylcholine-rich regions within the bilayer. Experiments with native ganglioside GM1, primarily a mixture of C18:1 and C20:1 long chain bases, indicate that the individual components of the mixture maintain their characteristic behavior within the lipid bilayer matrix. These results, together with the presence of a phase transition in native GM1 micellar dispersions, absent in purified C18:1 or C20:1 ganglioside micelles, strengthen the idea of a possible role of chain length composition in the modulation of ganglioside function.
Vitamin K-dependent carboxylase: possible role of the substrate "propeptide" as an intracellular recognition site. (1987)

The liver microsomal vitamin K-dependent carboxylase catalyzes the posttranslational conversion of specific glutamate residues to gamma-carboxyglutamate residues in a limited number of proteins. A number of these proteins have been shown to contain a homologous basic amino acid-rich "propeptide" between the leader sequence and the amino terminus of the mature protein. Plasmids encoding protein C, a vitamin K-dependent protein, containing or lacking a propeptide region were constructed and the protein was expressed in Escherichia coli. The protein products were assayed as substrates in an in vitro vitamin K-dependent carboxylase system. Only proteins containing a propeptide region were substrates for the enzyme. These data support the hypothesis that this sequence of the primary gene product is an important recognition site for this processing enzyme.
[Screening of angiotensin converting enzyme inhibitors from Salvia miltiorrhizae]. (2004)

S. miltiorrhiza inhibits angiotensin converting enzyme and its active components are in aqueous extract, in which the main were salvianolic acids including salvianolic acids B.
Removal of zinc layers from coated steel strip by thermal and mechanical processing (1999)

In this research project, basic investigations on the low temperature reactions of the zinc coating layer with the iron substrate were performed in order to develop novel methods for zinc removal from scrap material by baking the material at a moderate temperature to produce brittle intermetallic compounds, which may be subsequently removed under mechanical load, for instance by shredder treatment. The investigations have shown that it is possible to prepare a fragile Fe/Zn-intermetallic layer on the substrate by proper baking of the material at moderate temperatures. Mechanical working removes zinc from the strip substrate. The plane of cleavage is the phase boundary between the δ- and the Γ-compound. A precise control of the heating cycle adjusted to the layer thickness is mandatory to attain an effective zinc removal. This requirement is difficult to meet in the operation of an industrial installation. Im Rahmen dieses Forschungsprojektes wurden Grundlagenuntersuchungen zu den Reaktionen der Beschichtung mit der Eisenunterlage durchgeführt, um die Entwicklung neuer Methoden zur Entfernung von Zink aus Stahlschrott zu ermöglichen. Ziel ist die Erzeugung brüchiger intermetallischer Phasen durch Wärmebehandlung bei mittlerer Temperatur, die danach - z.B. durch Shreddern - entfernt werden können. Die Untersuchungen haben gezeigt, daß es möglich ist, geeignete intermetallische Phasenschichten des Systems Fe-Zn bei niedrigen Temperaturen zu erzeugen. Mechanische Bearbeitung führt zur Ablösung dieser Schichten. Die Trennebene ist die Phasengrenze zwischen 8- und Γ-Phase. Eine genaue Kontrolle der Wärmebehandlung, angepaßt an die Dicke der Auflageschicht, ist erforderlich, um eine wirksame Entzinkung zu erzielen. Dies ist in einem technischen Prozeß schwierig zu erreichen.
The avatar navigation of distributed virtual environment by using multiview client (2002)

The multi participant VR system can more enhance the sense of reality than existing single user VR systems. But, we should be careful when designing the system, since the current Internet using TCP/IP cannot afford to deliver such a massive amount of information required for the real time constraint of a VR system. We introduce distributed network structure and protocols for multiple user virtual space navigation and interaction through their avatars. This network structure is composed of heterogeneous multi servers, multiview clients and protocols. The multiview client can give proper information to the avatar when navigating the distributed virtual environment. And, for minimizing traffic on the network, we designed the VSTP-the Virtual Space Transfer Protocol to meet real time constraints. The avatars have nine behaviors and recognize the state of each other by using the pre-defined VSTP protocol.
Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy. (1994)

In order to assess the contamination with malignant cells of peripheral blood stem cell (PBSC) transplants used to support high-dose therapy in multiple myeloma (MM), we used the immunoglobulin heavy chain gene radioactive fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in PBSC from 10 patients. The sensitivity of the technique allowed the detection of one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was detected in 4 of 11 leukaphereses samples. The level of contamination was low because a clonal band could never be identified on ethidium bromide-stained agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony stimulatory factor (G-CSF) in combination with chemotherapy in three cases did not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was used during a second course of leukapheresis which was free of detectable clonal cells whereas the first one performed after chemotherapy alone contained clonal cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially malignant cells but the level of contamination is much lower than in BM grafts. Whether graft contamination is an important adverse prognostic factor for patients with MM undergoing intensive treatment and autografting is still unsettled.
Effects of Oral Supplementation with Cystine and Theanine on the Immune Function of Athletes in Endurance Exercise: Randomized, Double-Blind, Placebo-Controlled Trial (2009)

Athletes become increasingly susceptible to infection with intense training that results in immune suppression. The immune state was investigated after administering cystine/theanine (CT), which has been reported to have an immune reinforcement effect, to athletes before training involving a prolonged period of intense exercise. Fifteen long-distance runners were each allocated to the CT or placebo group, and the test food was ingested for 10 d prior to the start of training. Clinical examinations were performed before and after the training. The results indicate a significant increase in the high-sensitivity C-reactive protein (hs-CRP) and neutrophil count in the blood, as well as a decreasing tendency for lymphocytes in the placebo group, but not the CT group. These observations suggest that the ingestion of CT contributed to suppressing the change in inflammatory response, prevented a decrease in the immune function, and prevented infection and reduced symptoms when infected associated with continuous intense exercise.
Ussani's <i>Odes of Horace</i> - Le Liriche di Orazio. Commentate da Vincenzo Ussani. 2 vols. Torino: E. Loescher. 1900, 1901. Fr. 4.80. (1902)

An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Developmental expression of the axonal glycoprotein TAG-1: differential regulation by central and peripheral neurons <i>in vitro</i> (1991)

TAG-1 is a 135,000 Mr axonal glycoprotein of the immunoglobulin superfamily that promotes axon extension in vitro. One distinguishing feature of TAG-1 is its transient expression on subsets of axons in the developing nervous system. To examine the mechanisms that regulate TAG-1, we have monitored the expression of this protein by developing central and peripheral neurons in vitro. TAG-1 was detected on the surface of a subset of E11 to E13 spinal cord neurons in vitro and was also released by these neurons. Expressions of TAG-1 on the cell surface was transient but it was possible to detect a released form of TAG-1 at all times in vitro. Spinal cord neurons isolated from older embryos did not express surface TAG-1 when they regenerated axons in vitro. Changes in the environment of spinal cord neurons did not alter the time course of TAG-1 expression, suggesting that regulation of the protein is cell autonomous. In contrast to these results with spinal cord neurons, surface expression of TAG-1 by DRG neurons persisted in vitro and adult DRG neurons re-expressed TAG-1 when grown in vitro. The cell surface and released forms of TAG-1 therefore appear to be regulated differently by central and peripheral neurons.
A New Systematization of the Conformational Behavior of Seven-Membered Rings. Isoclinal Anomeric and Related Orientations<sup>1</sup> (1997)

The chair and twist-chair conformations of seven-membered rings are classified as a function of the signs of their endocyclic torsion angles. The conformational analysis (MM3) of the methoxy- and methyloxepanes 1-6 used as patterns allows the study and classification of the different types of hydrogen orientation in the seven-membered saturated heterocycles. General principles are established, allowing the prediction of the stability of the different twist-chair conformations as a function of the substituent type, its position in the ring, and the type of hydrogen atom that has been substituted. These results are extended to the 1,4-dioxepane derivatives 7-13 and are compared with experimental data.
Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt- 3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries (1993)

The expression patterns of four genes that are potential regulators of development were examined in the CNS of the embryonic day 12.5 mouse embryo. Three of the genes, Dlx-1, Dlx-2 (Tes-1), and Gbx-2, encode homeodomain-containing proteins, and one gene, Wnt-3, encodes a putative secreted differentiation factor. These genes are expressed in spatially restricted transverse and longitudinal domains in the embryonic neural tube, and are also differentially expressed within the wall of the neural tube. Dlx-1 and Dlx-2 are expressed in two separate regions of the forebrain in an identical pattern. The Gbx-2 gene is expressed in four domains, two of which share sharp boundaries with the domains of the Dlx genes. One boundary is in the basal telecephalon between deep and superficial strata of the medial ganglionic eminence; the other boundary is in the diencephalon at the zona limitans intrathalamica. The Wnt-3 gene is expressed in a dorsal longitudinal zone extending from the hindbrain into the diencephalon, where its expression terminates at the zona limitans intrathalamica. Reciprocal patterns of expression are found within the dorsal thalamus for the Gbx-2 and Wnt-3 genes. These findings are consistent with neuromeric theories of forebrain development, and based upon them we suggest a model for forebrain segmentation.
High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum (2000)

Chronic carriers of hepatitis B virus (HBV) usually show hepatitis B surface antigen (HBsAg) in their sera, which is considered the best marker for acute and chronic HBV infection. In some individuals, however, this antigen cannot be detected by routine serological assays despite the presence of virus in liver and peripheral blood. One reason for this lack of HBsAg might be mutations in the part of the molecule recognized by specific antibodies. To test this hypothesis, the HBV S gene sequences were determined of isolates from 33 virus carriers who were negative for HBsAg but showed antibodies against the virus core (anti-HBc) as the only serological marker of hepatitis B. Isolates from 36 HBsAg-positive patients served as controls. In both groups, a considerable number of novel mutations were found. In isolates from individuals with anti-HBc reactivity only, the variability of the major hydrophilic loop of HBsAg, the main target for neutralizing and diagnostic antibodies, was raised significantly when compared with the residual protein (22·6 vs 9·4 mutations per 1000 amino acids; P <0·001) and with the corresponding region in the controls (22·6 vs 7·5 exchanges per 1000 residues; P <0·001). A similar hypervariable spot was identified in the reverse transcriptase domain of the viral polymerase, encoded by the same nucleotide sequence in an overlapping reading frame. These findings suggest that at least some of the chronic low-level carriers of HBV, where surface antigen is not detected, could be infected by diagnostic escape mutants and/or by variants with impaired replication.
Mental and Psychical SciencesChallenging Current Beliefs (1992)

Although Newcomb was confident of the conceptual foundations of modern science, he did question the reliability of some of the superstructures built on them, and thus attempted to discredit the common belief in “scientific materialism”—the belief that mental phenomena could be reduced to physical processes. Similarly, he sought to debunk the growing belief in what might be called “scientific spiritualism”—the belief that psychic phenomena could be attributed to new and unseen processes operating in, for example, the ether. These probings of the superstructure of science, of scientific materialism and scientific spiritualism, are merely modest examples of Newcomb operating on our first level of methodological rhetoric. They are only modest examples because, although Newcomb was employing methodological pronouncements to discredit emerging and still-controversial theories of perceived scientific merit, he was neither grappling with theories of central concern to practicing natural scientists nor always directing his remarks to his professional colleagues.
Use of a Fluorescently Labeled Poly-Caspase Inhibitor for <i>in Vivo</i> Detection of Apoptosis Related to Vascular-Targeting Agent Arsenic Trioxide for Cancer Therapy (2007)

Arsenic trioxide (ATO, Trisenox) is a potent anti-vascular agent and significantly enhances hyperthermia and radiation response. To understand the mechanism of the anti-tumor effect in vivo we imaged the binding of a fluorescently-labeled poly-caspase inhibitor (FLIVO) in real time before and 3 h or 24 h after injection of 8 mg/kg ATO. FSaII tumors were grown in dorsal skin-fold window chambers or on the rear limb and we observed substantial poly-caspase binding associated with vascular damage induced by ATO treatment at 3 and 24 h after ATO injection. Flow cytometric analysis of cells dissociated from the imaged tumor confirmed cellular uptake and binding of the FLIVO probe. Apoptosis appears to be a major mode of cell death induced by ATO in the tumor and the use of fluorescently tagged caspase inhibitors to assess cell death in live animals appears feasible to monitor and/or confirm anti-tumor effects of therapy.
In Vitro Control of T-Lymphocyte Insulin Receptors by In Vivo Modulation of Insulin (1983)

The mechanism for carbohydrate intolerance related to insulin resistance is under intense study. Some have suggested that environmental modulation of plasma insulin concentrations may influence cellular mechanisms that could result in diminished receptor binding and thus create insulin resistance. We have employed the T-lymphocyte model to explore this possibility. Two groups of studies were performed. In the first, relative hyperinsulinemia was created in patients with type I diabetes mellitus by means of continuous subcutaneous insulin infusion by a portable insulin infusion device. In response to an elevation of “free” plasma insulin from 14 ± 2 to 26 ± 3 μU/ml there was a progressive fall in the number of insulin receptors that developed on freshly isolated, then lectin-treated, cultured T-lymphocytes (6552 ± 377 to 3241 ± 348 sites/cell) after 14 days of hyperinsulinemia. Neither the level of lectin stimulation, as ascertained by 3H-thy-midine uptake, nor the time course of response to PHA was altered by the insulin therapy. In the second study, plasma insulin was reduced in normal-weight subjects and in nondiabetic obese subjects (nearly twice ideal body weight) by means of a 4-day fast. In response to a fall in plasma insulin of 35 ± 6 to 19 ± 3 μU/ml, insulin receptor number on freshly isolated, then cultured and stimulated, lymphocytes rose from 2796 ± 379 sites/cell to 6453 ± 893 sites/cell. Again, neither a change in lectin responsiveness nor a change in the time course of PHA response accounted for the change in these data. The relationships between the direction and magnitude of changes in in vivo plasma insulin levels in both studies were analyzed together. There was a strong (r = 0.94; P &lt; 0.001) inverse relationship between changes in plasma insulin levels and the ultimate number of insulin receptors displayed on cultured lymphocytes. We conclude that in vivo insulin modulation is important for the regulation of the appearance of insulin receptors on cultured T-lymphocytes. Since the T-cell does not bear an insulin receptor in the circulation, the regulatory signals cannot be passed to this cell by the binding event itself. These data are not explained by a shift in a subset of lymphocytes present or by alterations in the degree of cell activation induced by PHA. The T-lymphocyte capacity to synthesize insulin receptors appears to be set, in part, by ambient plasma insulin concentrations.