gebhart/patrepeval huggingface dataset:
Induction of cell-mediated immune responses to human immunodeficiency virus type 1 Gag protein by using Listeria monocytogenes as a live vaccine vector (1995)

Cytolytic T cells, acting through cytokines or by direct lysis of infected target cells, have been shown to play a significant role in the control of viral infections and may be responsible for the prolonged asymptomatic phase following infection by HIV. Accordingly, methods that can generate strong cell-mediated immune responses may be useful in the development of prophylactic and therapeutic vaccines against HIV. Listeria monocytogenes is a Gram-positive intracellular microorganism that elicits strong cell-mediated immune responses against its own secreted proteins following infection. In this study we have modified the chromosome of L. monocytogenes so that it stably expresses and secretes the p55 HIV gag gene product and examined the cell-mediated immune response of BALB/c mice to infection with this recombinant organism. Infected animals were found to mount a specific, strong, long-lasting CD8+ cytolytic T cell response against a predominant epitope contained within the p24 fragment of the HIV Gag protein. This epitope previously has been shown to be recognized by CTLs obtained from some HIV-infected humans. Our results suggest that chromosomally modified strains of L. monocytogenes may provide valuable vaccine vectors for use against HIV.
Abstract 3725: Anti-DLL4 (demcizumab) inhibits tumor growth and reduces cancer stem cell frequency in patient-derived ovarian cancer xenografts. (2013)

Abstract Ovarian cancer in a major cause cancer related death in women and this disease is often characterized by resistance to chemotherapy and tumor recurrence. Cancer stem cells (CSCs) have been shown to be relatively insensitive to chemotherapeutic agents. Several lines of evidence indicate that aberrant Notch signaling plays a major role in ovarian cancer progression and resistance to standard therapies. DLL4 is a key ligand that activates the Notch pathway and has been shown to regulate both CSC function and tumor angiogenesis. DLL4 expression in tumor and endothelial cells has also been associated with resistance to bevacizumab treatment. In these studies, we investigated the role of anti-DLL4 in a panel of patient-derived ovarian cancer xenograft models. We utilized anti-human DLL4 (OMP-21M18) and anti-murine DLL4 to block Notch signaling in both the tumor and stromal/vascular cells in the xenografts. We found that anti-DLL4 treatment was broadly efficacious in these ovarian cancer models, significantly inhibiting tumor growth both as a single agent and in combination with paclitaxel. We carried out serial transplantation studies to investigate the effect on cancer stem cells and found that anti-DLL4 in combination with paclitaxel profoundly reduced the tumor initiating cell frequency. In contrast, treatment with paclitaxel alone had the opposite effect and increased ovarian CSC frequency. These data suggest that anti-DLL4 treatment sensitizes chemoresistant ovarian tumorigenic cells to therapy and provide compelling evidence that anti-DLL4 (demcizumab) is a promising strategy for the clinical treatment of ovarian cancer. Citation Format: Wan-Ching Yen, Marcus M. Fischer, Jalpa Shah, Jie Wei, Jennifer Cain, Pete Yeung, Lucia Beviglia, Belinda Cancilla, Ann Kapoun, John Lewicki, Austin Gurney, Timothy Hoey. Anti-DLL4 (demcizumab) inhibits tumor growth and reduces cancer stem cell frequency in patient-derived ovarian cancer xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3725. doi:10.1158/1538-7445.AM2013-3725
Lymph Node Fibroblastic Reticular Cells Construct the Stromal Reticulum via Contact with Lymphocytes (2004)

The sophisticated microarchitecture of the lymph node, which is largely supported by a reticular network of fibroblastic reticular cells (FRCs) and extracellular matrix, is essential for immune function. How FRCs form the elaborate network and remodel it in response to lymphocyte activation is not understood. In this work, we established ERTR7(+)gp38(+)VCAM-1(+) FRC lines and examined the production of the ER-TR7 antigen. Multiple chemokines produced by FRCs induced T cell and dendritic cell chemotaxis and adhesion to the FRC surface. FRCs can secrete the ER-TR7 antigen as an extracellular matrix component to make a reticular meshwork in response to contact with lymphocytes. The formation of the meshwork is induced by stimulation with tumor necrosis factor-alpha or lymphotoxin-alpha in combination with agonistic antibody to lymphotoxin-beta receptor in a nuclear factor-kappaB (RelA)-dependent manner. These findings suggest that signals from lymphocytes induce FRCs to form the network that supports the movement and interactions of immune effectors within the lymph node.
In Vitro Selection of Hammerhead Ribozymes Containing a Bulged Nucleotide in Stem II (1996)

Hammerhead ribozymes were transcribed from a dsDNA template containing four random nucleotides between stems II and III, which replace the naturally occurring GAA nucleotides. In vitro selection was used to select hammerhead ribozymes capable of in cis cleavage using denaturing polyacrylamide gels for the isolation of cleaving sequences. Self-cleaving ribozymes were cloned after the first and second rounds of selection, sequenced and characterised. Only sequences containing 5'-HGAA-3', where H is A, C or U, between stems II and III were active; G was clearly not tolerated at this position. Thus, only three sequences out of the starting pool of 256 (4(4)) were active. The Michaelis-Menten parameters were determined for the in trans cleaving versions of these ribozymes and indicate that selected ribozymes are less efficient than the native sequence. We propose that the selected ribozymes accommodate the extra nucleotide as a bulge in stem II.
Identification of Two Transcription Activation Units in the N-terminal Domain of the Human Androgen Receptor (1995)

To locate in detail the regions in the human androgen receptor (AR) involved in transcription activation, a series of N-terminal deletions was introduced in the wild type AR and in a constitutively active AR. The different constructs were tested for their capacity to activate transcription. Almost the entire N-terminal domain (residues 1-485) was necessary for full wild type AR activity when cotransfected with the (GRE)2tkCAT reporter in HeLa cells. In contrast, a smaller part of the N-terminal domain (amino acids 360-528) was sufficient for the constitutively active AR to induce transcription of the same (GRE)2tkCAT reporter in HeLa cells. This demonstrates the capacity of the AR to use different regions in the N-terminal domain as transcription activation units (TAUs). To obtain additional information of AR N-terminal TAUs, the GAL4 DNA binding domain was linked to either the entire or parts of the AR N-terminal domain and cotransfected with the (UAS)2tkCAT reporter in HeLa cells. The results confirmed that the first 485 amino acid residues accommodate a transcription activation function. When the chimeric AR-GAL4 constructs were tested on a different reporter ((UAS)5E1bCAT), a small shift in position of the TAU, responsible for full transcription activation, was observed. The data presented show that the size and location of the active TAU in the human AR is variable, being dependent on the promoter context and the presence or absence of the ligand binding domain.
Molecular Cloning of GA 2-Oxidase3 from Spinach and Its Ectopic Expression in Nicotiana sylvestris (2005)

Previous work has shown that 13-hydroxylated gibberellins (GAs) are predominant in the long-day (LD) plant spinach (Spinacia oleracea; GA53, GA44, GA19, GA20, GA1, GA8, and GA29). Also present in spinach are 2-hydroxylated C20-GAs: GA97, GA98, GA99, and GA110. Levels of the most abundant GA, GA97, decreased when plants were transferred from short photoperiods (SD) to LD. When [14C]GA53 was fed to spinach plants, more GA53 was converted to GA97 in SD than in LD, and more radioactive GA20 was formed in LD than in SD. SoGA2ox3, encoding a GA 2-oxidase, was isolated from spinach. The recombinant protein converted only two C20-GA precursors, GA12 and GA53, to their respective products, GA110 and GA97. GA2ox3 competes with GA20ox1 for their common substrate, GA53. In SD, deactivation to GA97 prevails, whereas in LD conversion to GA20 is favored. Transcript levels of SoGA2ox3 were higher in shoot tips than in blades, petioles, and young leaves. Ectopic expression of SoGA2ox3 in the long-day plant Nicotiana sylvestris showed a range of dwarf phenotypes, such as reduced germination, short hypocotyl and stem, dark-green leaves, and late flowering, but normal flowers and seed production. The levels of GA53 and GA1 were 3- to 5-fold lower in transgenic plants than in wild type, whereas the levels of GA97 and GA110 increased 3- to 6-fold in transgenic plants. It is concluded that genetic manipulation of plant stature by increasing deactivation of precursors of active GA is more advantageous than increased deactivation of bioactive GA1 itself.
Type II Antifreeze Protein from a Mid-latitude Freshwater Fish, Japanese Smelt (Hypomesus nipponensis) (2003)

A lot of reports of antifreeze protein (AFP) from fish have been published, but no report has mentioned of commercialized mid-latitude fresh water fish which producing AFP in its body fluid. We found that the AFP in the body fluid of Japanese smelt (Hypomesus nipponensis) from mid-latitude fresh water was purified and characterized. The N-terminal amino acid sequence of the Japanese smelt AFP was 75.0% identical to Type II AFP from herring. Results of EDTA treatment and ruthenium red staining suggested that the Japanese smelt AFP had at least one Ca2+-binding domain. Interestingly, the antifreeze activity of the Japanese smelt AFP did not completely disappear when Ca2+ ions were removed. The molecular mass of the Japanese smelt AFP was calculated to be 16,756.8 by the TOF-mass analysis. The Open reading flame of the gene coding for the Japanese smelt AFP was 444 bp long and was 85.0% identical with the entire herring AFP gene. The cDNA and amino acid sequence of the Japanese smelt AFP were the same length as those of herring AFP.
Mechanisms of proteasome inhibitor PS-341-induced G(2)-M-phase arrest and apoptosis in human non-small cell lung cancer cell lines. (2003)

Our data suggest that the PS-341-induced G(2)-M-phase arrest may be associated with the inhibition of degradation of cell cycle regulators and that the up-regulation of p21(cip/waf-1) expression may be via p53-dependent and/or -independent pathways. The resulting disturbance of cell cycle progression leads either to growth inhibition or to the initiation of apoptotic pathways.
Ultrathin Gold Nanoframes through Surfactant-Free Templating of Faceted Pentagonal Silver Nanoparticles (2011)

Ultrathin gold nanoframes (up to 1.6 nm) were prepared via templating upon well-defined faceted silver morphologies. Starting with silver decahedra, small quantities of gold (1-10 mol% relative to the amount of silver) were selectively deposited on the nanoparticle edges under optimized reducing conditions. Silver dissolution in hydrogen peroxide yielded well-defined gold frames that retained their structural integrity in the ultrathin nanowire regime below 2 nm. The frame formation protocol was also successfully applied to other silver nanoparticle shapes featuring pentagonal twinning and (111) facets (e.g., pentagonal faceted rods and icosahedra). The demonstrated approach can be applied in the controlled preparation of ultrathin metal nanowires complementary to lithography and in the production of ultrafine noble-metal nanostructures for catalytic applications.
String and module integrated inverters for single-phase grid connected photovoltaic systems - a review (2004)

This work presents an overview on recent developments and a summary of the state-of-the-art in inverter technology for single-phase grid connected photovoltaic (PV) systems. The information provided includes details on commercially available European string and module integrated PV inverters, their efficiency, price trends and market share. This review is given for inverters for a power level up to 6 kW. Furthermore, the paper deals with the recent developments of new inverter topologies and PV system concepts and discusses possible future trends.
Autoantibodies against granulocyte colony‐stimulating factor in Felty's syndrome and neutropenic systemic lupus erythematosus (2002)

Anti-G-CSF autoantibodies are common in neutropenia due to FS and SLE. In individual patients, these autoantibodies have a neutralizing capacity. In patients without neutralizing antibodies, hyposensitivity of the myeloid cells to G-CSF appears to be central to the pathogenesis of the neutropenia in FS and SLE.
Gene expression profiles of small-cell lung cancers: Molecular signatures of lung cancer (2006)

To characterize the molecular mechanisms involved in the carcinogenesis and progression of small-cell lung cancer (SCLC) and identify molecules to be applied as novel diagnostic markers and/or for development of molecular-targeted drugs, we applied cDNA microarray profile analysis coupled with purification of cancer cells by laser-microbeam microdissection (LMM). Expression profiles of 32,256 genes in 15 SCLCs identified 252 genes that were commonly up-regulated and 851 transcripts that were down-regulated in SCLC cells compared with non-cancerous lung tissue cells. An unsupervised clustering algorithm applied to the expression data easily distinguished SCLC from the other major histological type of non-small cell lung cancer (NSCLC) and identified 475 genes that may represent distinct molecular features of each of the two histological types. In particular, SCLC was characterized by altered expression of genes related to neuroendocrine cell differentiation and/or growth such as ASCL1, NRCAM, and INSM1. We also identified 68 genes that were abundantly expressed both in advanced SCLCs and advanced adenocarcinomas (ADCs), both of which had been obtained from patients with extensive chemotherapy treatment. Some of them are known to be transcription factors and/or gene expression regulators such as TAF5L, TFCP2L4, PHF20, LMO4, TCF20, RFX2, and DKFZp547I048 as well as those encoding nucleotide-binding proteins such as C9orf76, EHD3, and GIMAP4. Our data provide valuable information for better understanding of lung carcinogenesis and chemoresistance.
The dystrophin gene is alternatively spliced throughout its coding sequence (2002)

We have analysed splicing patterns in the human dystrophin gene region encoding the rod and cysteine-rich domains in normal skeletal muscle, brain and heart tissues. Sixteen novel alternative transcripts were identified, the majority of them being present in all three tissues. Tissue-specific variants were also identified, suggesting a functional role of transcriptional diversity. Transcript analysis in dystrophinopathic autoptic and bioptic specimens revealed that pre-mRNAs secondary structure formation and relative strength of exon/exon association play little or no role in directing alternative splicing events. This analysis also showed that independent deletion events leading to the loss of the same exons may be associated with transcriptional variability.
Infrastructure mediated sensing (2008)

Ubiquitous computing application developers have limited options for a practical activity and location sensing technology that is easy-to-deploy and cost-effective. In this dissertation, I have developed a class of activity monitoring systems called infrastructure mediated sensing (IMS), which provides a whole-house solution for sensing activity and the location of people and objects. Infrastructure mediated sensing leverages existing home infrastructure (e.g., electrical systems, air conditioning systems, etc.) to mediate the transduction of events. In these systems, infrastructure activity is used as a proxy for a human activity involving the infrastructure. A primary goal of this type of system is to reduce economic, aesthetic, installation, and maintenance barriers to adoption by reducing the cost and complexity of deploying and maintaining the activity sensing hardware. I discuss the design, development, and applications of various IMS-based activity and location sensing technologies that leverage the following existing infrastructures: wireless Bluetooth signals, power lines, and central heating, ventilation, and air conditioning (HVAC) systems. In addition, I show how these technologies facilitate automatic and unobtrusive sensing and data collection for researchers or application developers interested in conducting large-scale in-situ location-based studies in the home.
A protein-domain microarray identifies novel protein–protein interactions (2002)

Protein domains mediate protein-protein interactions through binding to short peptide motifs in their corresponding ligands. These peptide recognition modules are critical for the assembly of multiprotein complexes. We have arrayed glutathione S-transferase (GST) fusion proteins, with a focus on protein interaction domains, on to nitrocellulose-coated glass slides to generate a protein-domain chip. Arrayed protein-interacting modules included WW (a domain with two conserved tryptophans), SH3 (Src homology 3), SH2, 14.3.3, FHA (forkhead-associated), PDZ (a domain originally identified in PSD-95, DLG and ZO-1 proteins), PH (pleckstrin homology) and FF (a domain with two conserved phenylalanines) domains. Here we demonstrate, using peptides, that the arrayed domains retain their binding integrity. Furthermore, we show that the protein-domain chip can 'fish' proteins out of a total cell lysate; these domain-bound proteins can then be detected on the chip with a specific antibody, thus producing an interaction map for a cellular protein of interest. Using this approach we have confirmed the domain-binding profile of the signalling molecule Sam68 (Src-associated during mitosis 68), and have identified a new binding profile for the core small nuclear ribonucleoprotein SmB'. This protein-domain chip not only identifies potential binding partners for proteins, but also promises to recognize qualitative differences in protein ligands (caused by post-translational modification), thus getting at the heart of signal transduction pathways.
“Chemical Transformers” from Nanoparticle Ensembles Operated with Logic (2008)

The pH-responsive nanoparticles were coupled with information-processing enzyme-based systems to yield "smart" signal-responsive hybrid systems with built-in Boolean logic. The enzyme systems performed AND/OR logic operations, transducing biochemical input signals into reversible structural changes (signal-directed self-assembly) of the nanoparticle assemblies, thus resulting in the processing and amplification of the biochemical signals. The hybrid system mimics biological systems in effective processing of complex biochemical information, resulting in reversible changes of the self-assembled structures of the nanoparticles. The bioinspired approach to the nanostructured morphing materials could be used in future self-assembled molecular robotic systems.
Hematopoietic prostaglandin D2synthase controls the onset and resolution of acute inflammation through PGD2and 15-deoxyΔ12–14PGJ2 (2007)

Hematopoietic prostaglandin D(2) synthase (hPGD(2)S) metabolizes cyclooxygenase (COX)-derived PGH(2) to PGD(2) and 15-deoxyDelta(12-14) PGJ(2) (15d-PGJ(2)). Unlike COX, the role of hPGD(2)S in host defense is ambiguous. PGD(2) can be either pro- or antiinflammatory depending on disease etiology, whereas the existence of 15d-PGJ(2) and its relevance to pathophysiology remain controversial. Herein, studies on hPGD(2)S KO mice reveal that 15d-PGJ(2) is synthesized in a self-resolving peritonitis, detected by using liquid chromatography-tandem MS. Together with PGD(2) working on its DP1 receptor, 15d-PGJ(2) controls the balance of pro- vs. antiinflammatory cytokines that regulate leukocyte influx and monocyte-derived macrophage efflux from the inflamed peritoneal cavity to draining lymph nodes leading to resolution. Specifically, inflammation in hPGD(2)S KOs is more severe during the onset phase arising from a substantial cytokine imbalance resulting in enhanced polymorphonuclear leukocyte and monocyte trafficking. Moreover, resolution is impaired, characterized by macrophage and surprisingly lymphocyte accumulation. Data from this work place hPGD(2)S at the center of controlling the onset and the resolution of acute inflammation where it acts as a crucial checkpoint controller of cytokine/chemokine synthesis as well as leukocyte influx and efflux. Here, we provide definitive proof that 15d-PGJ(2) is synthesized during mammalian inflammatory responses, and we highlight DP1 receptor activation as a potential antiinflammatory strategy.
Human immunodeficiency virus type 1 RNA expression by four chronically infected cell lines indicates multiple mechanisms of latency (1994)

Recent information has suggested that posttranscriptional mechanisms, whereby human immunodeficiency virus type 1 (HIV-1) RNA exists as multiply spliced transcripts without promoting an accumulation of the larger messages, are responsible for maintaining a stable state of nonproductive viral expression or viral latency. To test the universality of these observations, we compared the patterns of viral RNA splicing and the frequencies of cells actually harboring HIV-1 RNA in four chronically HIV-1-infected cell lines (U1 [promonocytic], ACH-2 [T lymphocytic], OM-10.1 [promyelocytic], and J1.1 [T lymphocytic]). In uninduced U1 and ACH-2 cultures, a high frequency of cells (approximately one in six) contained HIV-1 RNA but mainly as multiply spliced transcripts, again supporting a posttranscriptional mechanism maintaining viral latency. In sharp contrast, only 1 in 50 cells in uninduced OM-10.1 and J1.1 cultures contained HIV-1 RNA, indicating a primary transcriptional mechanism controlling viral expression in these cells. Furthermore, those OM-10.1 and J1.1 cells that did contain viral RNA were in a state of productive HIV-1 expression marked by the presence of both spliced and unspliced transcripts. Even though the total absence of viral RNA in the majority of OM-10.1 and J1.1 cells indicated a state of absolute latency, treatment with tumor necrosis factor alpha induced transcription of HIV-1 RNA in nearly 100% of the cells in all four of the chronically infected cultures. Tumor necrosis factor alpha induction of U1, ACH-2, and OM-10.1 cultures resulted in an initial accumulation of multiply spliced HIV-1 RNA followed by a transition to the larger unspliced viral RNA transcripts. This RNA splice transition was less apparent in the J1.1 cell line. These results demonstrate that host cell-specific transcriptional and posttranscriptional mechanisms are important factors in the control of HIV-1 latency.