gebhart/patrepeval huggingface dataset:
Early detection of ovarian cancer using group biomarkers (2008)

One reason that ovarian cancer is such a deadly disease is because it is not usually diagnosed until it has reached an advanced stage. In this study, we developed a novel algorithm for group biomarkers identification using gene expression data. Group biomarkers consist of coregulated genes across normal and different stage diseased tissues. Unlike prior sets of biomarkers identified by statistical methods, genes in group biomarkers are potentially involved in pathways related to different types of cancer development. They may serve as an alternative to the traditional single biomarkers or combination of biomarkers used for the diagnosis of early-stage and/or recurrent ovarian cancer. We extracted group biomarkers by applying biclustering algorithms that we recently developed on the gene expression data of over 400 normal, cancerous, and diseased tissues. We identified several groups of coregulated genes that encode for secreted proteins and exhibit expression levels in ovarian cancer that are at least 2-fold (in log2 scale) higher than in normal ovary and nonovarian tissues. In particular, three candidate group biomarkers exhibited a conserved biological pattern that may be used for early detection or recurrence of ovarian cancer with specificity greater than 99% and sensitivity equal to 100%. We validated these group biomarkers using publicly available gene expression data sets downloaded from a NIH Web site (http://www.ncbi.nlm.nih.gov/geo). Statistical analysis showed that our methodology identified an optimum combination of genes that have the highest effect on the diagnosis of the disease compared with several computational techniques that we tested. Our study also suggests that single or group biomarkers correlate with the stage of the disease.
In Vivo Messenger RNA Introduction into the Central Nervous System Using Polyplex Nanomicelle (2013)

Messenger RNA (mRNA) introduction is a promising approach to produce therapeutic proteins and peptides without any risk of insertion mutagenesis into the host genome. However, it is difficult to introduce mRNA in vivo mainly because of the instability of mRNA under physiological conditions and its strong immunogenicity through the recognition by Toll-like receptors (TLRs). We used a novel carrier based on self-assembly of a polyethylene glycol (PEG)-polyamino acid block copolymer, polyplex nanomicelle, to administer mRNA into the central nervous system (CNS). The nanomicelle with 50 nm in diameter has a core-shell structure with mRNA-containing inner core surrounded by PEG layer, providing the high stability and stealth property to the nanomicelle. The functional polyamino acids possessing the capacity of pH-responsive membrane destabilization allows smooth endosomal escape of the nanomicelle into the cytoplasm. After introduction into CNS, the nanomicelle successfully provided the sustained protein expression in the cerebrospinal fluid for almost a week. Immune responses after mRNA administration into CNS were effectively suppressed by the use of the nanomicelle compared with naked mRNA introduction. In vitro analyses using specific TLR-expressing HEK293 cells confirmed that the nanomicelle inclusion prevented mRNA from the recognition by TLRs. Thus, the polyplex nanomicelle is a promising system that simultaneously resolved the two major problems of in vivo mRNA introduction, the instability and immunogenicity, opening the door to various new therapeutic strategies using mRNA.
Contribution of the mannan O side-chains to the adjuvant action of lipopolysaccharides. (1987)

Klebsiella 03 lipopolysaccharide (LPS) and Escherichia coli 09 LPS were previously shown to have potent adjuvant activities in augmenting antibody response and delayed-type hypersensitivity to protein antigens. The R form LPS extracted from the O-specific polysaccharide-less mutants derived from Klebsiella 03 and E. coli 09 strains were characterized by chemical and electrophoretic analyses. The adjuvant activities of the R-LPS in augmenting antibody response and DTH to protein antigens were much weaker than those of the parental LPS. The strength of the adjuvant activities of the R-LPS was similar to that of the activities of Salmonella minnesota LPS and Ra-LPS. By contrast, polyclonal B-cell activation effects of the R-LPS were stronger than those of the parental LPS. The common feature of the parental LPS is that their O-specific polysaccharides are mannose homopolymers (mannans). From these results, it is suggested that mannose homopolymers as the O side-chains of LPS contribute to the action of LPS in enhancing strongly the T-cell dependent immune responses to protein antigens.
Simple optimization method of one-dimensional M-PAM constellations for the AWGN channels (2003)

This paper presents a simple method optimization of one-dimensional M-ary pulse amplitude modulation (M-PAM) constellations for the additive white Gaussian noise (AWGN) channels when the error probability is minimized under the power constraint. This method is independent of the distribution information source, and adapts the given source M-PAM signal constellation for transmission on the AWGN channel.
Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody That Recognizes a Novel Conformational Epitope on gp41 and Lacks Reactivity against Self-Antigens (2008)

Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics.
Targeting the Replication Checkpoint Using SCH 900776, a Potent and Functionally Selective CHK1 Inhibitor Identified via High Content Screening (2011)

Checkpoint kinase 1 (CHK1) is an essential serine/threonine kinase that responds to DNA damage and stalled DNA replication. CHK1 is essential for maintenance of replication fork viability during exposure to DNA antimetabolites. In human tumor cell lines, ablation of CHK1 function during antimetabolite exposure led to accumulation of double-strand DNA breaks and cell death. Here, we extend these observations and confirm ablation of CHK2 does not contribute to these phenotypes and may diminish them. Furthermore, concomitant suppression of cyclin-dependent kinase (CDK) activity is sufficient to completely antagonize the desired CHK1 ablation phenotypes. These mechanism-based observations prompted the development of a high-content, cell-based screen for γ-H2AX induction, a surrogate marker for double-strand DNA breaks. This mechanism-based functional approach was used to optimize small molecule inhibitors of CHK1. Specifically, the assay was used to mechanistically define the optimal in-cell profile with compounds exhibiting varying degrees of CHK1, CHK2, and CDK selectivity. Using this approach, SCH 900776 was identified as a highly potent and functionally optimal CHK1 inhibitor with minimal intrinsic antagonistic properties. SCH 900776 exposure phenocopies short interfering RNA-mediated CHK1 ablation and interacts synergistically with DNA antimetabolite agents in vitro and in vivo to selectively induce dsDNA breaks and cell death in tumor cell backgrounds.
Characterization of clonogenic stromal cells isolated from human endometrium (2008)

Human endometrium is an object of extensive restructuring and remodeling during the female reproductive life and it is quite tempting to assume that these periodic changes happen with the participation of cells that should have the basic characteristics of multipotent cells. The aim of this study was to search for the presence of cells with plastic adherence, clonogenicity, and differentiation in human endometrium. To this end, human endometrial stromal cells were cultured in vitro for more than 15 passages. Flow cytometry analysis of the cultured cells showed that they were positive for CD29, CD73 and CD90, which are considered to be the markers of cells with mesenchymal origin. The cells were negative for the hematopoietic cell markers (CD45, CD34, CD14, CD3, CD19, CD16/56, and HLA-DR). Further, it was shown that the cultured cells had 15% clonogenic efficiency and could be induced to differentiate into adipogenic cells containing typical lipid-rich vacuoles. These results demonstrate that the human endometrium contains a low number of cells with the characteristics of endometrial stromal stem/progenitor cells, which seem to belong to the family of the mesenchymal stem cells. It can be speculated that these cells are engaged into the monthly restructuring and remodeling of human endometrium.
Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model (2004)

We tested the hypothesis that microtubule (MT)-binding drugs could be therapeutically beneficial in tauopathies by functionally substituting for the MT-binding protein tau, which is sequestered into inclusions of human tauopathies and transgenic mouse models thereof. Transgenic mice were treated for 12 weeks with weekly i.p. injections of 10 or 25 mg/m(2) paclitaxel (Paxceed). Both doses restored fast axonal transport in spinal axons, wherein MT numbers and stable (detyrosinated) tubulins were increased, compared with sham treatment, and only Paxceed ameliorated motor impairments in tau transgenic mice. Thus, MT-stabilizing drugs could have therapeutic potential for treating neurodegenerative tauopathies by offsetting losses of tau function that result from the sequestration of this MT-stabilizing protein into filamentous inclusions.
FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice (2005)

We report the characterization of factor inhibiting activating transcription factor 4 (ATF4)-mediated transcription (FIAT), a leucine zipper nuclear protein. FIAT interacted with ATF4 to inhibit binding of ATF4 to DNA and block ATF4-mediated transcription of the osteocalcin gene in vitro. Transgenic mice overexpressing FIAT in osteoblasts also had reduced osteocalcin gene expression and decreased bone mineral density, bone volume, mineralized volume, trabecular thickness, trabecular number, and decreased rigidity of long bones. Mineral homeostasis, osteoclast number and activity, and osteoblast proliferation and apoptosis were unchanged in transgenics. Expression of osteoblastic differentiation markers was largely unaffected and type I collagen synthesis was unchanged. Mineral apposition rate was reduced in transgenic mice, suggesting that the lowered bone mass was due to a decline in osteoblast activity. This cell-autonomous decrease in osteoblast activity was confirmed by measuring reduced alkaline phosphatase activity and mineralization in primary osteoblast cultures. These results show that FIAT regulates bone mass accrual and establish FIAT as a novel transcriptional regulator of osteoblastic function.
Generating hypermedia documents from transcriptions of television programs using parallel text alignment (2002)

This paper presents a method of automatically creating hypermedia documents from conventional transcriptions of television programs. Using parallel text alignment techniques, the temporal information derived from the closed caption signal is exploited to convert the transcription into a synchronized text stream. Given this text stream, we can create links between the transcription and the image and audio media streams. We describe a two-pass method for aligning parallel texts that first uses dynamic programming techniques to maximize the number of corresponding words (by minimizing the word edit distance). The second stage converts the word alignment into a sentence alignment, taking into account the cases of sentence split and merge. We present results of text alignment on a database of 610 programs (including three television news programs over a one-year period) for which we have closed caption, transcript, audio and image streams. The techniques presented can produce high quality hypermedia documents of video programs with little or no additional manual effort.
Requirement of Pyk2 for the activation of the MAP kinase cascade induced by Ca2+ (but not by PKC or G protein) in PC12 cells (1999)

The role of the Ca(2+)-activated tyrosine kinase, Pyk2, in the pleiotropic coupling of nerve cell stimulation to the MAP kinase cascade still remains undefined. Using a panel of PC12 clones, one of which was defective in Pyk2, we demonstrate (1) that the MAP kinase response induced by a [Ca(2+)](i) rise (following application of the Ca(2+) ionophore, ionomycin) is inappreciable in the defective clone and is re-established after Pyk2 transfection; and (2) that the responses to both protein kinase C and P(2y2) receptor activation occur normally even in the defective cells. We conclude that Pyk2 is the key mediator in the pathway activated by Ca(2+) but has minor roles with the other types of stimulation.
An introduction to spinors (2013)

We introduce spinors, at a level appropriate for an undergraduate or first year graduate course on relativity, astrophysics or particle physics. The treatment assumes very little mathematical knowledge (mainly just vector analysis and some idea of what a group is). The SU(2)--SO(3) homomorphism is presented in detail. Lorentz transformation, chirality, and the spinor Minkowski metric are introduced. Applications to electromagnetism, parity violation, and to Dirac spinors are presented. A classical form of the Dirac equation is obtained, and the (quantum) prediction that $g=2$ for Dirac particles is presented.
[Expression of TPO mimetic peptide chimeric proteins with human IgG1 Fc fragments and their biological characters]. (2002)

Many antineoplastic agents can cause myelosuppression and thrombocytopenia. Thrombopoietin (TPO) is believed to be the major cytokine affecting the proliferation and maturation of megakaryocytes and increasing circulating platelet levels. We have designed and synthesized a TPO mimetic peptide, it can increase circulating platelet levels in vivo. For increasing half-life and forming dimer, the peptide was expressed as chimeric proteins with human IgG1 Fc fragments. The cDNA of TPO mimetic peptide was synthesized chemically and linked respectively to 5' terminus of human IgG1 Fc cDNA fragments in various length (Fc1: Fc 5' 648 bp; Fc2: Fc 5' 270 bp; Fc3: Fc 5' 267 bp; Fc4: Fc 5' 90 bp), and cloned into expression plasmid pET28a (+) for constructing four recombinant plasmids. By transforming the four recombinant plasmids into E. coli. BL21 (DE3) respectively, we got 3 kinds of engineered E. coli which express TPO + Fc chimeric proteins(28 kD TPO + Fc1, 12 kD TPO + Fc2 and 12 kD TPO + Fc3) at high level respectively, the expressed proteins were purified with DEAE-Sepharose FF and S-Sepharose FF column. The bioactivities of the expressed chimeric proteins(TPO + Fc1, TPO + Fc2 and TPO + Fc3), TPO mimetic peptide, and PEG4000 coupled TPO mimetic peptide were evaluated with Ba/F3-mp1 in vitro and with carboplatin-induced thrombocytopenia mice in vivo, the expressed chimeric proteins have higher activity than TPO mimetic peptide both in vitro and in vivo, the EC50 on Ba/F3-mp1 cells were 13, 10, 10, 50, and 25 nmol/L respectively, all of them can increase circulating platelet counts. Their imol/Lunogenicity were valuated in mice, none of them can elicit mice to produce antibodies to TPO mimetic peptide, meanwhile three TPO + Fc chimeric proteins can elicit mice to produce antibodies to human IgG1 Fc. These studies have laid basis for production of TPO mimetic peptide by genetic engineering.
High-Grade Undifferentiated Small Round Cell Sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 Fusion: Emerging Entities of Soft Tissue Tumors with Unique Histopathologic Features – A Case Report and Literature Review (2015)

Background:A subset of undifferentiated small round cell sarcomas (USRCSs) is currently being recognized as emerging entities with unique gene fusions: CIC-DUX4 (the area of focus in this article), BCOR-CCNB3, or CIC-FOXO4 gene fusions. CIC-DUX4 and CIC-FOXO4 fusions have been reported in soft tissue tumors, while BCOR-CCNB3 fusion with an X chromosomal inversion was described in both bone and soft tissue tumors. CIC-DUX4 fusion can either harbor t(4;19)(q35;q13.1) or t(10;19)(q26.3;q13), while t(4;19)(q35;q13.1) is reported more commonly. Case Report:The aim of this study is to share a new case report of a 36-year-old woman who had a rapidly growing mass in her right upper thigh, which was found to be an undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion was confirmed by cytogenetic testing. Combined modality treatment with surgery, radiation, and chemotherapy was used and achieved a good response. A review of the literature of the reported cases with CIC-DUX4 fusions including both t(4;19) and t(10;19) translocations revealed a total of 44 cases reported. Out of these 44 cases, 33 showed t(4;19)(q35;q13.1) translocation compared to 11 cases with t(10;19)(q26.3;q13). Conclusions:Undifferentiated small round cell sarcomas are aggressive tumors. Their treatment includes surgery, chemotherapy, and radiation. Resistance to chemotherapy is common. Lung and brain are common sites of metastasis, with associated poor prognosis. Generally, median survival is less than 2 years. Newer techniques have been developed recently which helped identify a subset of previously unclassifiable sarcomas, with promising prognostic value.
Characterization of a Trimeric Complex Containing Oct-1, SNAPc, and DNA (1997)

The human small nuclear (sn) RNA promoters contain a proximal sequence element (PSE), which recruits the basal transcription factor SNAPc, and a distal sequence element characterized by an octamer sequence, which recruits the POU domain transcription factor Oct-1. The Oct-1 POU domain and SNAPc bind cooperatively to probes containing a PSE and an octamer sequence, and this effect contributes to efficient transcription in vitro. In vivo, however, Oct-1 regions outside of the POU domain can activate snRNA gene transcription. Here, we have examined whether the role of these regions is to contribute to cooperative binding with SNAPc. We find that they indeed improve cooperative binding, but most of the effect is nevertheless mediated by just the POU domain. This suggests that Oct-1 activates transcription of snRNA genes in at least two steps, recruitment of SNAPc mediated primarily by the POU domain, and a later step mediated by regions outside of the POU domain. We also show that a PSE-binding complex observed in nuclear extracts consists of Oct-1 and SNAPc. Although Oct-1 cannot bind effectively to the PSE probe on its own, in the complex it contacts DNA. Thus, in a nuclear extract, SNAPc can recruit Oct-1 to a probe to which Oct-1 cannot bind on its own.
Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells (2012)

We have previously shown that broadly neutralizing antibodies reactive to the conserved stem region of the influenza virus hemagglutinin (HA) were generated in people infected with the 2009 pandemic H1N1 strain. Such antibodies are rarely seen in humans following infection or vaccination with seasonal influenza virus strains. However, the important question remained whether the inactivated 2009 pandemic H1N1 vaccine, like the infection, could also induce these broadly neutralizing antibodies. To address this question, we analyzed B-cell responses in 24 healthy adults immunized with the pandemic vaccine in 2009. In all cases, we found a rapid, predominantly IgG-producing vaccine-specific plasmablast response. Strikingly, the majority (25 of 28) of HA-specific monoclonal antibodies generated from the vaccine-specific plasmablasts neutralized more than one influenza strain and exhibited high levels of somatic hypermutation, suggesting they were derived from recall of B-cell memory. Indeed, memory B cells that recognized the 2009 pandemic H1N1 HA were detectable before vaccination not only in this cohort but also in samples obtained before the emergence of the pandemic strain. Three antibodies demonstrated extremely broad cross-reactivity and were found to bind the HA stem. Furthermore, one stem-reactive antibody recognized not only H1 and H5, but also H3 influenza viruses. This exceptional cross-reactivity indicates that antibodies capable of neutralizing most influenza subtypes might indeed be elicited by vaccination. The challenge now is to improve upon this result and design influenza vaccines that can elicit these broadly cross-reactive antibodies at sufficiently high levels to provide heterosubtypic protection.
Scanning Electrochemical Microscopy of Metal/Metal Oxide Electrodes. Analysis of Spatially Localized Electron-Transfer Reactions during Oxide Growth (1999)

Scanning electrochemical microscopy (SECM) has been used to study the oxidation of iodide at Ta electrodes covered by a thin (∼2.5 nm) film of Ta(2)O(5). SECM images of surface activity reveal that the voltammetric response of a macroscopic Ta electrode comprises the individual responses of a large number of microscopic sites, each with its own unique electrochemical behavior. Oxide film growth and metal dissolution occur simultaneously with iodide oxidation, resulting in a complex voltammetric response. The component of the voltammetric current due to iodide oxidation can be separated from the total current by SECM analysis. The growth of nanometer-thick oxide films can also be studied using SECM by monitoring the rate at which iodide is oxidized at the electrode surface.
Bonding of cartilage matrices with cultured chondrocytes: An experimental model (1998)

The capacity of isolated chondrocytes to join separate masses of cartilage matrix was investigated with composites implanted in subcutaneous pouches in nude mice. Slices of articular cartilage were harvested from lambs and were devitalized by cyclic freezing and thawing. The slices were then either co-cultured with viable allogeneic lamb chondrocytes (experimental) or cultured without such chondrocytes (control). Composites of three slices were constructed with use of fibrin glue and were implanted in nude mice for periods ranging from 7 to 42 days. Bonding of the experimental matrices with viable chondrocytes was achieved at 28 and 42 days, as assessed by direct examination, histology, thymidine uptake, and fluorescence. No bonding occurred in the control composites without viable chondrocytes. We conclude that devitalized cartilage matrix is a scaffold to which isolated chondrocytes can attach and begin to repopulate.