gebhart/patrepeval huggingface dataset:
Development of novel PET probes, [18F]BCPP‐EF, [18F]BCPP‐BF, and [11C]BCPP‐EM for mitochondrial complex 1 imaging in the living brain (2013)

We developed three novel positron-emission tomography (PET) probes, 2-tert-butyl-4-chloro-5-{6-[2-(2[(18)F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([(18)F]BCPP-EF), 2-tert-butyl-4-chloro-5-[6-(4-[(18) F]fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one ([(18)F]BCPP-BF), and 2-tert-butyl-4-chloro-5-{6-[2-(2-[(11)C]methoxy-ethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([(11)C]BCPP-EM), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in vivo. These three PET probes were successfully labeled by nucleophilic [(18)F]fluorination or by [(11)C]methylation of their corresponding precursor with sufficient radioactivity yield, good radiochemical purity, and sufficiently high specific radioactivity for PET measurement. The specificity of these probes for binding to MC-1 was assessed with rotenone, a specific MC-1 inhibitor, by a rat brain slice imaging method in vitro. Rat whole-body imaging by small-animal PET demonstrated that all probes showed high uptake levels in the brain as well as in the heart sufficient to image them clearly. The rank order of uptake levels in the brain and the heart just after injection was as follows: high in [(18)F]BCPP-BF, intermediate in [(11)C]BCPP-EM, and low in [(18) F]BCPP-EF. The kinetics of [(18)F]BCPP-EF and [(11)C]BCPP-EM provided a reversible binding pattern, whereas [(18)F]BCPP-BF showed nonreversible accumulation-type kinetics in the brain and heart. Metabolite analyses indicated that these three compounds were rapidly metabolized in the plasma but relatively stable in the rat brain up to 60 min post-injection. The present study demonstrated that [(18)F]BCPP-EF could be a useful PET probe for quantitative imaging of MC-1 activity in the living brain by PET.
Soluble CD163: An age-dependent, anti-inflammatory biomarker predicting outcome in sepsis* (2006)

University Hospital Ulm, Ulm, Germany The authors have not disclosed any potential conflicts of interest.
Isolation of a proline-rich mycobacterial protein eliciting delayed-type hypersensitivity reactions only in guinea pigs immunized with living mycobacteria. (1993)

Effective protection against a virulent challenge with Mycobacterium tuberculosis is induced only by a previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). Living and killed bacteria share a number of common antigens. To identify and to purify molecules that are dominant antigens during immunization with living bacteria, a two-step selection procedure was used. Quantitative delayed-type hypersensitivity (DTH) reactions elicited in guinea pigs immunized either with living or with killed BCG were used to select or counterselect antigens present in BCG culture filtrates. Each major fraction eluted from a series of HPLC columns (gel filtration, DEAE, reverse-phase chromatography) was assayed and titrated on guinea pigs of each group. A protein with an unusual amino acid composition (40% proline, 12% threonine) was purified and N-terminally sequenced. To our knowledge, the sequence Thr-Pro-Pro-Xaa-Glu-Xaa-Pro-Pro-Pro-Pro-Gln-Xaa-Val-Xaa-Leu has not been previously reported. The protein was 100-fold more potent on guinea pigs immunized with living bacteria than on guinea pigs immunized with dead bacteria to elicit a DTH reaction.
Retinoic Acid Inhibition of Chromatin Remodeling at the Human Immunodeficiency Virus Type 1 Promoter (2004)

All-trans retinoic acid (RA) represses HIV-1 transcription and replication in cultured monocytic cells and in primary monocyte-derived macrophages. Here we examine the role of histone acetylation and chromatin remodeling in RA-mediated repression. RA pretreatment of latently infected U1 promonocytes inhibits HIV-1 expression in response to the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). TSA is thought to activate HIV-1 transcription by inducing histone hyperacetylation within a regulatory nucleosome, nuc-1, positioned immediately downstream from the transcription start site. Acetylation of nuc-1 is thought to be a critical step in activation that precedes nuc-1 remodeling and, subsequently, transcriptional initiation. Here we demonstrate that TSA treatment induces H3 and H4 hyperacetylation and nuc-1 remodeling. Although RA pretreatment inhibits nuc-1 remodeling and HIV-1 transcription, it has no effect on histone acetylation. This suggests that acetylation and remodeling are not obligatorily coupled. We also show that growth of U1 cells in retinoid-deficient medium induces nuc-1 remodeling and HIV-1 expression but does not induce histone hyperacetylation. These findings suggest that remodeling, not histone hyperacetylation, is the limiting step in transcriptional activation in these cells. Together, these data suggest that RA signaling maintains the chromatin structure of the HIV-1 promoter in a transcriptionally non-permissive state that may contribute to the establishment of latency in monocyte/macrophages.
The Relationship between Libido and Testosterone Levels in Aging Men (2006)

Libido and T concentrations are strongly related at the population level. However, the value of individual patient reports of reduced libido as indicators of low T levels is open to question.
Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells. (2000)

We have conjugated the murine monoclonal antibody (528) against the human epidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolene (2-IT). The conjugate showed dose-dependent cytotoxicity against EGFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detectable cytotoxicity against EGFR-deficient small-cell lung cancer cells (H69). The cytotoxicity of the conjugate was positively correlated with the EGFR numbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immunoconjugate might be useful for targeted treatment of squamous cell carcinomas hyperexpressing EGFR.
Evidence of Contextual Fear after Lesions of the Hippocampus: A Disruption of Freezing But Not Fear-Potentiated Startle (1997)

The roles of the dorsal hippocampus and the central nucleus of the amygdala in the expression of contextual fear were assessed using two measures of conditioned fear: freezing and fear-potentiated startle. A discriminable context conditioning paradigm was developed that demonstrated both conditioned freezing and fear-potentiated startle in a context paired previously with foot shock, relative to a context in which foot shock had never been presented. Post-training lesions of the central nucleus of the amygdala completely blocked both contextual freezing and fear-potentiated startle. Post-training lesions of the dorsal hippocampus attenuated contextual freezing, consistent with previous reports in the literature; however, these same lesions had no effect on fear-potentiated startle, suggesting preserved contextual fear. These results suggest that lesions of the hippocampus disrupt the freezing response but not contextual fear itself.
Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma (1991)

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.
Genome-scale analysis of DNA methylation in colorectal cancer using Infinium HumanMethylation450 BeadChips (2013)

Illumina's Infinium HumanMethylation450 BeadChip arrays were used to examine genome-wide DNA methylation profiles in 22 sample pairs from colorectal cancer (CRC) and adjacent tissues and 19 colon tissue samples from cancer-free donors. We show that the methylation profiles of tumors and healthy tissue samples can be clearly distinguished from one another and that the main source of methylation variability is associated with disease status. We used different statistical approaches to evaluate the methylation data. In general, at the CpG-site level, we found that common CRC-specific methylation patterns consist of at least 15,667 CpG sites that were significantly different from either adjacent healthy tissue or tissue from cancer-free subjects. Of these sites, 10,342 were hypermethylated in CRC, and 5,325 were hypomethylated. Hypermethylated sites were common in the maximum number of sample pairs and were mostly located in CpG islands, where they were significantly enriched for differentially methylated regions known to be cancer-specific. In contrast, hypomethylated sites were mostly located in CpG shores and were generally sample-specific. Despite the considerable variability in methylation data, we selected a panel of 14 highly robust candidates showing methylation marks in genes SND1, ADHFE1, OPLAH, TLX2, C1orf70, ZFP64, NR5A2, and COL4A. This set was successfully cross-validated using methylation data from 209 CRC samples and 38 healthy tissue samples from The Cancer Genome Atlas consortium (AUC = 0.981 [95% CI: 0.9677-0.9939], sensitivity = 100% and specificity = 82%). In summary, this study reports a large number of loci with novel differential methylation statuses, some of which may serve as candidate markers for diagnostic purposes.
E2Ls, E2F-like Repressors of Arabidopsis That Bind to E2F Sites in a Monomeric Form (2002)

E2F transcription factors are major regulators of cell proliferation, and each factor contributes differently to cell cycle control. Arabidopsis contains six E2F homologs, of which three are proteins that exhibit an overall similarity to animal E2Fs and interact with DPa and DPb to stimulate DNA binding. Here we describe the other three E2F-like proteins from Arabidopsis, E2L1-3, which have two copies of a domain with a limited similarity only to the DNA binding domain of E2F. Unlike known E2Fs, the three E2L proteins failed to interact with DPa and DPb and could efficiently bind E2F sites in a monomeric form through the dual-type domain. Transfection assays revealed that E2Ls repress the transcription of reporter genes under the control of E2F-regulated promoters, indicating that E2Ls function to antagonize transactivation mediated by E2F.DP. When fused to green fluorescence protein, E2L1 and E2L3 were predominantly localized to the nucleus whereas E2L2 was detected in both the nucleus and cytoplasm. Because the transcripts of E2Ls were abundant in meristematic rather than fully differentiated tissues, E2Ls may balance the activities of E2F.DP and play a role in restraining cell proliferation.
Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation. (1996)

Relapse remains a significant problem after allogeneic bone marrow transplantation (BMT). For patients with relapsed chronic myelogenous leukemia (CML), infusions of donor mononuclear cells (MNC) provide a potent graft-versus-leukemia (GVL) reaction inducing complete remissions in the majority of patients. Little is known about the efficacy of donor MNC infusions for patients who relapse with other diseases. We have studied the GVL effects of donor MNC in eight patients with relapsed acute leukemia or myelodysplasia (MDS). One patient with relapsed MDS achieved complete remission and another patient had a transient response. Five of six non-responders died of progressive leukemia and one non-responder died of complications during second BMT. Three patients developed grade I-II acute GVHD responsive to immunosuppression. These data, and review of the literature, suggest that GVL induction with donor MNC infusions is less effective for patients with relapsed acute leukemia than for patients with relapsed CML; too few patients with relapsed MDS have been treated to draw definite conclusions. However, some patients respond, and given the high mortality associated with alternative procedures such as second BMT, donor MNC infusions are a reasonable approach for relapsed acute leukemia and MDS after allogeneic BMT.
Biologic assay of a thrombosis-inducing activity in human serum (1959)

The systemic infusion of thrombin-free human serum induces massive thrombosis in rabbit vein segments containing stagnant blood far removed from the site of infusion. In contrast, carefully collected human plasma is inert in this system. The data indicate that this phenomenon of in vivo thrombosis is quantitatively related to the amount of serum infused and forms the basis for a bioassay of the thrombosis-inducing activity. This bioassay, in providing a technique for detecting and quantitating the thrombosis-inducing activity of normal human serum, may facilitate separation of this activity from other recognized coagulation factors and serve as a guide to its ultimate isolation, purification and characterization. Note: (With the Technical Assistance of Marjorie Nickles, Mary-Lou Bloede, Bela J. Szalai and Rita J. Nickerson) Submitted on June 18, 1959
Bandgap-Engineered Ga-Rich GaZnO Thin Films for UV Transparent Electronics (2009)

Ga-rich GaZnO thin films were prepared by metal-organic chemical vapor deposition. The optical bandgap of GaZnO films can be engineered from 3.3 to 4.9 eV by varying the Ga content. The film is amorphortized and the resistivity increases with an increase of Ga content. The Ga-rich GaZnO alloy with lower resistivity is investigated as a UV transparent conductor, while the semi-insulating Ga-rich GaZnO film with high transparency at 280-900 nm is employed as the channel layer to fabricate deep UV transparent thin-film transistor. The transistor shows a typical n-channel field-effect characteristic with a current on/off ratio of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> - 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> , a threshold voltage of ~42 V, a saturated field-effect mobility of ~0.06 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> middot V <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> middot s <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> , and a subthreshold swing of ~7.7 V middot decade <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> .
Using input command pre-shaping to suppress multiple mode vibration (2002)

Spacecraft, space-borne robotic systems, and manufacturing equipment often utilize lightweight materials and configurations that give rise to vibration problems. Prior research has led to the development of input command preshapers that can significantly reduce residual vibration. These shapers exhibit marked insensitivity to errors in natural frequency estimates and can be combined to minimize vibration at more than one frequency. A method for the development of multiple mode input shapers which are simpler to implement than previous designs and produce smaller system response delays is presented. The new technique involves the solution of a group of simultaneous nonlinear impulse constraint equations. The resulting shapers were tested on a model of MACE, an MIT/NASA experimental flexible structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reliable Blast UDP : predictable high performance bulk data transfer (2003)

High speed bulk data transfer is an important part of many data-intensive scientific applications. This paper describes an aggressive bulk data transfer scheme, called Reliable Blast UDP (RBUDP), intended for extremely high bandwidth, dedicated- or Quality-of-Service-enabled networks, such as optically switched networks. This paper also provides an analytical model to predict RBUDP's performance and compares the results of our model against our implementation of RBUDP. Our results show that RBUDP performs extremely efficiently over high speed dedicated networks and our model is able to provide good estimates of its performance.
99mTc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors (2007)

Detection of HER2-overexpression in tumors and metastases is important for the selection of patients who will benefit from trastuzumab treatment. Earlier investigations showed successful imaging of HER2-positive tumors in patients using indium- or gallium-labeled Affibody molecules. The goal of this study was to evaluate the use of (99m)Tc-labeled Affibody molecules for the detection of HER2 expression. The Affibody molecule Z(HER2:342) with the chelator sequences mercaptoacetyl-Gly-Glu-Gly (maGEG) and mercaptoacetyl-Glu-Glu-Glu (maEEE) was synthesized by peptide synthesis and labeled with technetium-99m. Binding specificity, cellular retention, and in vitro stability were investigated. The biodistribution of (99m)Tc-maGEG-Z(HER2:342) and (99m)Tc-maEEE-Z(HER2:342) was compared with (99m)Tc-maGGG-Z(HER2:342) in normal mice, and the tumor targeting properties of (99m)Tc-maEEE-Z(HER2:342) were determined in SKOV-3 xenografted nude mice. The results showed that the Affibody molecules were efficiently labeled with technetium-99m. The labeled conjugates were highly stable in vitro with preserved HER2-binding capacity. The use of glutamic acid in the chelator sequences for (99m)Tc-labeling of Z(HER2:342) reduced the hepatobiliary excretion 3-fold with a single Gly-to-Glu substitution and 10-fold with three Gly-to-Glu substitutions. (99m)Tc-maEEE-Z(HER2:342) showed a receptor-specific tumor uptake of 7.9 +/- 1.0 %IA/g and a tumor-to-blood ratio of 38 at 4 h pi. Gamma-camera imaging with (99m)Tc-maEEE-Z(HER2:342) could detect HER2-expressing tumors in xenografts already at 1 h pi. It was concluded that peptide synthesis for the coupling of chelator sequences to Affibody molecules for (99m)Tc labeling is an efficient way to modify the in vivo kinetics. Increased hydrophilicity, combined with improved stability of the mercaptoacetyl-triglutamyl chelator, resulted in favorable biodistribution, making (99m)Tc-maEEE-Z(HER2:342) a promising tracer for clinical imaging of HER2 overexpression in tumors.
On migrating a legacy application to the palm platform (2004)

Handheld computing devices such as personal digital assistants (PDAs) and the latest mobile phones are becoming widespread, so migrating desktop applications to these platforms is of great interest to developers. However, little information is available to guide the novice especially for the palm OS, the,most popular platform in the PDA and smartphone arena. This paper highlights the migration challenges involved and potential directions in easing this reengineering process. To explore the practical understanding and reengineering issues, a large legacy application was partially migrated to palm OS.
Molecular Subtyping of Primary Prostate Cancer Reveals Specific and Shared Target Genes of Different ETS Rearrangements (2012)

This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa), namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1) and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2) was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B) was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.
Antiproliferative Effects of Octadecyloxyethyl 9-[2-(Phosphonomethoxy)Ethyl]Guanine against Me-180 Human Cervical Cancer Cells in vitro and in vivo (2010)

ODE-PMEG may be suitable for local or topical treatment of cervical dysplasia.
Suspended Animation in C. elegans Requires the Spindle Checkpoint (2003)

In response to environmental signals such as anoxia, many organisms enter a state of suspended animation, an extreme form of quiescence in which microscopically visible movement ceases. We have identified a gene, san-1, that is required for suspended animation in Caenorhabditis elegans embryos. We show that san-1 functions as a spindle checkpoint component in C. elegans. During anoxia-induced suspended animation, embryos lacking functional SAN-1 or a second spindle checkpoint component, MDF-2, failed to arrest the cell cycle, exhibited chromosome missegregation, and showed reduced viability. These data provide a model for how a dynamic biological process is arrested in suspended animation.
Automatic Data Structure Repair for Self-Healing Systems (2003)

We have developed a system that accepts a specification of key data structure constraints, then dynamically detects and repairs violations of these constraints, enabling the program to recover from otherwise crippling errors to continue to execute productively. We present our experience using our system to repair violated constraints in a simplified version of the ext2 file system and in the CTAS air-traffic control program. Our experience indicates that the specifications are relatively straightforward to develop and that our technique enables the applications to effectively recover from data structure corruption errors. 1.