gebhart/patrepeval huggingface dataset:
Direct Analysis and MALDI Imaging of Formalin-Fixed, Paraffin-Embedded Tissue Sections (2007)

Formalin fixation, generally followed by paraffin embedding, is the standard and well-established processing method employed by pathologist. This treatment conserves and stabilizes biopsy samples for years. Analysis of FFPE tissues from biopsy libraries has been, so far, a challenge for proteomics biomarker studies. Herein, we present two methods for the direct analysis of formalin-fixed, paraffin-embedded (FFPE) tissues by MALDI−MS. The first is based on the use of a reactive matrix, 2,4-dinitrophenylhydrazine, useful for FFPE tissues stored less than 1 year. The second approach is applicable for all FFPE tissues regardless of conservation time. The strategy is based on in situ enzymatic digestion of the tissue section after paraffin removal. In situ digestion can be performed on a specific area of the tissue as well as on a very small area (microdigestion). Combining automated microdigestion of a predefined tissue array with either in situ extraction prior to classical nanoLC/MS−MS analysis or automated microspotting of MALDI matrix according to the same array allows the identification of both proteins by nanoLC-nanoESI and MALDI imaging. When adjacent tissue sections are used, it is, thus, possible to correlate protein identification and molecular imaging. These combined approaches, along with FFPE tissue analysis provide access to massive amounts of archived samples in the clinical pathology setting. Keywords: MALDI • Imaging • FFPE • in situ enzymatic digestion
Simulations of transient membrane behavior in cells subjected to a high-intensity ultrashort electric pulse (2005)

A molecular dynamics (MD) scheme is combined with a distributed circuit model for a self-consistent analysis of the transient membrane response for cells subjected to an ultrashort (nanosecond) high-intensity (approximately 0.01-V/nm spatially averaged field) voltage pulse. The dynamical, stochastic, many-body aspects are treated at the molecular level by resorting to a course-grained representation of the membrane lipid molecules. Coupling the Smoluchowski equation to the distributed electrical model for current flow provides the time-dependent transmembrane fields for the MD simulations. A good match between the simulation results and available experimental data is obtained. Predictions include pore formation times of about 5-6 ns. It is also shown that the pore formation process would tend to begin from the anodic side of an electrically stressed membrane. Furthermore, the present simulations demonstrate that ions could facilitate pore formation. This could be of practical importance and have direct relevance to the recent observations of calcium release from the endoplasmic reticulum in cells subjected to such ultrashort, high-intensity pulses.
Phosphorylation of PKC activation loop plays an important role in receptor‐mediated translocation of PKC (2005)

Protein kinase C (PKC) is translocated to various cellular regions in a subtype and stimulation-dependent manner. Thereafter, the activated PKC phosphorylates its substrate and causes subsequent cellular responses (PKC targeting). The 3-phosphoinositide-dependent protein kinase-1 (PDK1) has an essential role in the maturation of PKC by phosphorylating a threonine residue in the PKC activation loop. To elucidate the role of PDK1 in PKC targeting, we expressed mutant gamma- or delta-PKC fused with GFP (gamma- or delta-PKC-ALM (activation loop mutant)-GFP), whose threonine residue in the activation loop was replaced with alanine, and compared their P2Y receptor-mediated translocation with wild-type PKC-GFP in CHO cells. ATP (1 mm) induced the transient translocation of wild-type gamma- or delta-PKC-GFP from cytoplasm to plasma membrane and following retranslocation from membrane to the cytoplasm. gamma- or delta-PKC-ALM-GFP was also translocated to plasma membrane, which was, however, retained at the membrane for a longer period than wild type. Similar results were observed in kinase-negative PKC mutants, indicating that the phosphorylation by PDK1 affects the retranslocation step of PKC by regulating the kinase activity. The simultaneous monitoring of [Ca2+]i and diacylglycerol (DG) levels with the translocation of PKC demonstrated that PKC-ALM induced the prolonged accumulation of DG, resulting in the prolonged retention of PKC-ALM at the plasma membrane. It is possible that PKC-ALM with decreased kinase activity could delay the conversion of DG at the plasma membrane. Our present study suggests that the activation loop phosphorylation plays an important role in receptor-mediated PKC targeting.
Total Synthesis of Sialylgalactosylgloboside:  Stage-Specific Embryonic Antigen 4 (1996)

A versatile total synthesis of sialylgalactosylgloboside (SGG, 1), carrying the stage-specific embryonic antigen 4 (SSEA-4) is reported, illustrating a more general strategy for the synthesis of complex globo-series glycosphingolipids. Starting from readily available building blocks 7, 8, and 10, two different approaches to the synthesis of the key tetrasaccharide 6 have been developed in a highly convergent manner. Further glycosylations with galactosyl trichloroacetimidate (5) and sialyl phosphite (2) donors successively afforded the penta- and hexasaccharides 3 and 11. The latter was finally converted into the target molecule (SGG, 1) with the help of a azidosphingosine glycosylation procedure, favored in this case by the stereocontrolling properties of the 2a-O-pivaloyl protecting group. Valuable intermediates 6 and 3, having the oligosaccharidic skeletons of Gb(4) and Gb(5) (SSEA-3), respectively, were obtained in the course of the synthesis.
Peer-to-Peer: Harnessing the Power of Disruptive Technologies (2001)

From the Publisher:
Upstart software projects Napster, Gnutella, and Freenet have dominated newspaper headlines, challenging traditional approaches to content distribution with their revolutionary use of peer-to-peer file-sharing technologies. Reporters try to sort out the ramifications of seemingly ungoverned peer-to-peer networks. Lawyers, business leaders, and social commentators debate the virtues and evils of these bold new distributed systems. But what's really behind such disruptive technologies -- the breakthrough innovations that have rocked the music and media worlds? And what lies ahead?
In this book, key peer-to-peer pioneers take us beyond the headlines and hype and show how the technology is changing the way we communicate and exchange information. Those working to advance peer-to-peer as a technology, a business opportunity, and an investment offer their insights into how the technology has evolved and where it's going. They explore the problems they've faced, the solutions they've discovered, the lessons they've learned, and their goals for the future of computer networking.
Until now, Internet communities have been limited by the flat interactive qualities of email and network newsgroups, where people can exchange recommendations and ideas but have great difficulty commenting on one another's postings, structuring information, performing searches, and creating summaries. Peer-to-peer challenges the traditional authority of the client/server model, allowing shared information to reside instead with producers and users. Peer-to-peer networks empower users to collaborate on producing and consuming information, adding to it, commenting on it, and building communities around it.
This compilation represents the collected wisdom of today's peer-to-peer luminaries. It includes contributions from Gnutella's Gene Kan, Freenet's Brandon Wiley, Jabber's Jeremie Miller, and many others -- plus serious discussions of topics ranging from accountability and trust to security and performance. Fraught with questions and promise, peer-to-peer is sure to remain on the computer industry's center stage for years to come.
GM‐CSF and Pregnancy: Evidence of Significantly Reduced Blood Concentrations in Unexplained Recurrent Abortion Efficiently Reverted by Intravenous Immunoglobulin Treatment (2003)

GM-CSF is found increased in normal pregnancy and is very low during pregnancy in RSA. IVIg infusions are capable of increasing GM-CSF in pregnant recurrent aborters.
Pregnenolone 16 alpha-carbonitrile-inducible P-450 gene family: gene conversion and differential regulation. (1986)

A cytochrome P-450 cDNA clone, designated pP450PCN2, homologous to the previously characterized pregnenolone 16 alpha-carbonitrile (PCN)-induced P-450 cDNA (pP450PCN1; F. J. Gonzalez, D. W. Nebert, J. P. Hardwick, and C. B. Kasper, J. Biol. Chem. 260:7435-7441), was isolated from a rat liver cDNA expression library by use of a polyclonal anti-P450PCN1 antibody. This P-450 cDNA contains 2,014 base pairs and yields an open reading frame of a protein consisting of 504 amino acids (Mr = 57,760). P450PCN2 cDNA and protein shared 90% nucleotide and 89% amino acid similarity with P450PCN1 cDNA and protein, respectively. The 5' untranslated, coding, and 3' untranslated regions between the two cDNAs share 94, 93, and 79% similarities, respectively. Nucleotide differences in the coding regions, however, are not evenly distributed. Complete homology exists between the two mRNAs for 425 nucleotides (positions 346 through 771). Other regions of 93 nucleotides containing only one difference and 147 nucleotides containing two differences exist toward the 3' end of the coding regions. These data suggest the possibility that a gene conversion event(s) have occurred subsequent to duplication of the ancestral P450PCN gene. Oligonucleotide probes unique for P450PCN1 and P450PCN2 cDNAs were used to examine the levels of their respective mRNAs in noninduced and PCN-induced liver cells and in male and female rats of various ages. P450PCN1 mRNA was not detectable in either male or female rats at any ages. In contrast, P450PCN2 mRNA was present at a low level in newborn rats and became elevated in both males and females at 1 week of age. Levels of p450PCN2 mRNA continued to increase in males until 12 weeks, whereas the mRNA in females reached peak levels at 2 weeks of age but declined continuously at the onset of puberty (between 4 and 12 weeks). These levels of P45PCN2 mRNA closely parallel the increases in testosterone 6 beta-hydroxylase activity and P450PCN2 protein level, as analyzed by Western blots. P450PCN1 mRNA was induced by PCN, dexamethasone, and phenobarbital in both male and female rats. P450PCN2 mRNA was not significantly induced by PCN or dexamethasone but was readily induced by phenobarbital. Testosterone 6 beta-hydroxylase activity was also induced severalfold by PCN, dexamethasone, and phenobarbital. These data demonstrate that P450PCN1 and P450PCN2 genes are differentially regulated during development and after administration of inducing compounds and furthermore suggest that both enzymes possess testosterone 6 beta-hydroxylase activity.
Synthetic Biodegradable Polymer Scaffolds (1997)

This body of work represents the first volume of a book series covering the field of tissue engineering. Tissue engineering, which refers to a category of therapeutic or diagnostic products and proces
High-Affinity Serum Growth-Hormone-Binding Protein, Absent in Laron-Type Dwarfism, Is Diminished in Heterozygous Parents (1990)

Human serum high-affinity growth-hormone-binding protein (GHBP), as determined by incubation with 125I-GH followed by chromatography on AcA 44 gel minicolumns, is lacking in patients with Laron-type dwarfism (LTD). We found that the specific binding of 125I-GH to high-affinity GHBP in normal human serum (m ± SD) was 11.5 ± 1.8% in 10 children 2–3 years old, 15.3 ± 2.2% in 10 children 5–8 years old, and 19.3 ± 2.9% in 15 adults 20–40 years old. It was 0.3% in a 2-year-old child with LTD, and 10.6 ± 11.3% in his parents. It was 0.1 % in another child with LTD, 7 years old, and 14.4 and 14.8% in his parents. The mean value in the heterozygous parents (12.8 ± 2.1%) was significantly lower (p < 0.001) than control values. A void volume peak (VVP) of radioactivity, corresponding to the so-called low-affinity GHBP which eluted at the void volume in chromatographs of normal sera remained unchanged with sera of patients with LTD or of their parents and appeared even after incubations of the tracer without serum. This study (1) shows that high-affinity GHBP is diminished in heterozygotes with LTD; (2) confirms that high-affinity GHBP and VVP are independently regulated, and (3) suggests that a part of the VVP may not be related to GH binding to some serum components.
Traumatic Brain Injury Induces Rapid Enhancement of Cortical Excitability in Juvenile Rats (2014)

Our results demonstrate that CCI in juvenile rats rapidly induces epileptiform activity and enhanced cortical synaptic bursting. Detection of epileptiform activity early after injury suggests it may be an important pathophysiological component and potential indicator of developing PTE.
Lanthanide‐based susceptibility contrast agents: Assessment of the magnetic properties (1996)

Abstract The T 2 * contrast efficacy of paramagnetic contrast agents is dependent on their magnetic properties. Vibrating sample magnetometry (VSM) and the Live Chan NMR method have been used to evaluate the influence of ligand structure on the bulk magnetic susceptibility (BMS) of low‐molecular weight (LMW) lanthanide chelates. VSM was also used for the BMS assessment of LMW lanthanide chelates covalentiy attached to cross‐linked starch particles. The ligand structure had no influence on the BMS of the gadolinium (Gd) and dysprosium (Dy) chelates. The mean BMS value of the Dychelates was 1.8 fold higher than that of the Gd‐chelates. The holmium (Ho) OTPA‐BMA chelate had a similar BMS to that of Dy‐DTPA‐BMA while the lowest BMS was found for europium (Eu(lll)) DTPA‐BMA. The covatent attachment of Gd‐DTPA and Dy‐DTPA to a cross‐linked starch particle had no impact on their intrinsic magnetic properties. The BMS data were in good accordance with those obtained for non‐particulate bound LMW Dy‐ and Gd‐chelates. The magnetic susceptibility of the Gd‐OTPA labeled particles was described by the Curie law, indicative of no magnetic interactions between Gd‐DTPA molecules. The magnetic susceptibility of the Dy‐DTPA labeled particles followed the Curie‐Weiss law with a Curie‐Weiss temperature of about ‐2 K, indicating magnetic interactions. The magnetic susceptibility of Dy‐DTPA will, however, not be affected by such magnetic interactions at physiological temperatures.
Photopatterning, Etching, and Derivatization of Self-Assembled Monolayers of Phosphonic Acids on the Native Oxide of Titanium (2009)

Electron-hole pair formation at titania surfaces leads to the formation of reactive species that degrade organic materials. Here, we describe the degradation of self-assembled monolayers of alkylphosphonic acids on the native oxide of titanium following exposure to UV light. The rate of degradation was found to decrease as the length of the adsorbate molecule increased. Increasing order in the monolayer, resulting from the enhanced dispersion forces between longer adsorbates, impedes the progress of oxygen-containing molecules to the oxide surface and slows the rate of oxidation. Rates of degradation on titanium oxide are substantially greater than rates of degradation on aluminum oxide because of the photocatalytic effect of the titanium oxide substrate. Micrometer-scale patterns may be fabricated readily using a UV laser in conjunction with a mask, and nanometer-scale patterns may be fabricated using a scanning near-field optical microscope coupled to a UV laser. Photodegraded adsorbates may be replaced by contrasting molecules to yield chemical contrast. Such patterned materials have been utilized to fabricate patterns from polymer nanoparticles. The resist character is switchable--at lower exposures, the monolayer behaves as a positive tone resist, but at higher exposures, it exhibits negative tone behavior. Patterned samples may also be utilized as resists for solution-phase etching of the underlying substrate.
Low Temperature Metal Induced Lateral Crystallization of Ge Using Germanide Forming Metals (2009)

10.1149/1.3264625
Induction of Th1 and Th2 CD4+ T cell responses by oral or parenteral immunization with ISCOMS (1995)

Abstract We examined the ability of oral or parenteral immunization with immune stimulating complexes containing ovalbumin (ISCOMS‐OVA) to prime T cell proliferative and cytokine responses. A single subcutaneous immunization with ISCOMS‐OVA primed potent antigen‐specific proliferative responses in the draining popliteal lymph node, which were entirely dependent on the presence of CD4 + T cells. CD8 + T cells did not proliferate in vitro even in the presence of the appropriate peptide epitope and exogenous interleukin (IL)‐2. Primed popliteal lymph node cells produced IL‐2, IL‐5 and interferon (IFN)‐γ, but not IL‐4 when restimulated with OVA in vitro. Serum antigen‐specific IgG1 and IgG2a antibody responses were also primed by subcutaneous immunization with ISCOMS‐OVA, confirming the stimulation of both Th1 and Th2 cells in vivo. Spleen cells from subcutaneously primed mice produced a similar pattern of cytokines, indicating that disseminated priming had occurred. Oral immunization with ISCOMS‐OVA also primed local antigen‐specific proliferative responses in the mesenteric lymph node and primed an identical pattern of systemic cytokine responses in the spleen. The ability of ISCOMS to prime both Th1 and Th2 CD4 + T cell responses may be central to their potent adjuvant activities and confirm the potential of ISCOMS as future oral vaccine vectors.
Characterization of a Novel, Membrane-bound, 80-kDa Matrix-degrading Protease from Human Breast Cancer Cells (1997)

A major, apparently novel extracellular matrix-degrading protease was previously identified and partially isolated from hormone-dependent but not from hormone-independent human breast cancer cells (Shi, Y. E., Torri, J., Yieh, L., Wellstein, A., Lippman, M. E., and Dickson, R. B. (1993) Cancer Res. 53, 1409-1415). Although initially the 80-kDa protease was identified from breast cancer cell-conditioned medium, immunofluorescence staining of breast cancer cells with anti-80-kDa protease monoclonal antibody 21-9 showed that in addition to its detection in intracellular compartments, the protease was uniformly localized around periphery of the cells with more intensive staining on the pseudopodia and membrane ruffles. A surface biotinylation technique confirmed the plasma membrane localization of the protease. In addition, the 80-kDa protease could not be washed from the membrane fraction of homogenized breast cancer cells with high concentrations of salts or with EDTA. The 80-kDa protease may noncovalently associate with other protein(s) to form complexes, the 95- and 110-kDa proteases. Both complexes showed gelatinolytic activity and bore the epitopes recognized by monoclonal antibody 21-9. Furthermore, both complexes could be converted to 80-kDa forms by boiling in SDS in the absence of reducing agents. Expression of this novel, integral membrane gelatinase could allow breast cancer cells an alternative to other previously described matrix-degrading enzymes for degradation of the extracellular matrix in close proximity to their surfaces.
Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. (1986)

This report describes the use of fluorescence in situ hybridization for chromosome classification and detection of chromosome aberrations. Biotin-labeled DNA was hybridized to target chromosomes and subsequently rendered fluorescent by successive treatments with fluorescein-labeled avidin and biotinylated anti-avidin antibody. Human chromosomes in human-hamster hybrid cell lines were intensely and uniformly stained in metaphase spreads and interphase nuclei when human genomic DNA was used as a probe. Interspecies translocations were detected easily at metaphase. The human-specific fluorescence intensity from cell nuclei and chromosomes was proportional to the amount of target human DNA. Human Y chromosomes were fluorescently stained in metaphase and interphase nuclei by using a 0.8-kilobase DNA probe specific for the Y chromosome. Cells from males were 40 times brighter than those from females. Both Y chromosomal domains were visible in most interphase nuclei of XYY amniocytes. Human 28S ribosomal RNA genes on metaphase chromosomes were distinctly stained by using a 1.5-kilobase DNA probe.
The BION devices: injectable interfaces with peripheral nerves and muscles (2006)

Injected microstimulators represent a promising new class of technology for the rehabilitation of patients with upper motor neuropathies. As the technology evolves, practitioners may be able to use it to facilitate functional reanimation of paralyzed limbs.
Biological Principles of Brain Tumor Immunotherapy (2001)

The objective of this chapter is to discuss the biological principles that currently guide the design of immunotherapies (ITs) directed against central nervous system (CNS) tumors. Direct translation of systemic ITs currently in use to CNS tumors is limited by the heterogeneity of gliomas, immunosuppression mediated by cytokines elaborated by gliomas, and the possible induction, in the case of nonspecific ITs, of potentially lethal autoimmune reactions. In order to design rational ITs, a clear knowledge of immunological responses within the CNS is required. The basic tenet of "immunological privilege" is placed within the more proper context of immunological suppression. Emerging concepts, such as antigen (Ag) presentation within the CNS and the presence of CNS complement, are presented as well, because these areas represent new potential areas for therapeutic intervention. Discussion of application of this information, including manipulation of cytokines, adoptive IT, vaccination, and tumor-specific Ag approaches, is reserved for other chapters.KeywordsExperimental Autoimmune EncephalomyelitisMalignant GliomaMyelin Basic ProteinExperimental Allergic EncephalomyelitisBiological PrincipleThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.