gebhart/patrepeval huggingface dataset:
PET probes for distinct metabolic pathways have different cell specificities during immune responses in mice (2010)

Clinical tools that measure changes in immune cell metabolism would improve the diagnosis and treatment of immune dysfunction. PET, utilizing probes for specific metabolic processes, detects regions of immune activation in vivo. In this study we investigated the immune cell specificity of PET probes for two different metabolic pathways: [18F]-2-fluorodeoxyglucose ([18F]-FDG) for glycolysis and [18F]-2-fluoro-D-(arabinofuranosyl)cytosine ([18F]-FAC) for deoxycytidine salvage. We isolated innate and adaptive immune cells from tissues of mice challenged with a retrovirus-induced sarcoma and measured their ability to accumulate FDG and FAC. We determined that the two probes had distinct patterns of accumulation: FDG accumulated to the highest levels in innate immune cells, while FAC accumulated predominantly in CD8+ T cells in a manner that correlated with cellular proliferation. This study demonstrates that innate and adaptive cell types differ in glycolytic and deoxycytidine salvage demands during an immune response and that these differential metabolic requirements can be detected with specific PET probes. Our findings have implications for the interpretation of clinical PET scans that use [18F]-FDG or [18F]-FAC to assess immune function in vivo and suggest potential applications of metabolic PET to monitor the effects of targeted immune modulation.
Androgen-Induced Inhibition of Proliferation in Human Breast Cancer MCF7 Cells Transfected with Androgen Receptor* (1997)

Sex steroids control the proliferation of their target cells through two different pathways: 1) proliferative response (Step-1); and 2) inhibition of cell proliferation (Step-2). Mechanisms of cell proliferation regulation are incompletely understood; however, there is general agreement with the notion that sex steroid receptors play an important role in the control of the proliferation of sex steroid target cells. To test this hypothesis, a full human androgen receptor (AR) vector was transfected into human breast cancer MCF7 cells. The cloned cells that stably express the AR, called MCF7-AR1 cells, contained approximately five times more AR than the wild-type MCF7 cells from which they were derived. These AR-transfected cells retained their capacity to proliferate when estrogens were added to 10% charcoal-dextran stripped human serum but did not acquire the ability to proliferate when androgens were added to this medium. In serumless medium (ITDME), these cells proliferated maximally, as MCF7 cells did; however, natural and synthetic androgens prevented the AR-transfected cells from proliferating. Inhibition of cell proliferation occurred when physiological androgen concentrations (1 nM) were added to ITDME; this effect was almost completely reversed by Casodex, a synthetic androgen antagonist. Under the effect of androgens added to ITDME, MCF7-AR1 cells were arrested in the G0/G1 phase within 24 h. These data suggest that: 1) the androgen-induced inhibition of cell proliferation (Step-2) is AR-mediated; and 2) the AR may be necessary, but not sufficient, to mediate the androgen-induced proliferative response (Step-1).
Variants in ASB10 are associated with open-angle glaucoma (2011)

The molecular events responsible for obstruction of aqueous humor outflow and the loss of retinal ganglion cells in glaucoma, one of the main causes of blindness worldwide, remain poorly understood. We identified a synonymous variant, c.765C>T (Thr255Thr), in ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) in a large family with primary open angle glaucoma (POAG) mapping to the GLC1F locus. This variant affects an exon splice enhancer site and alters mRNA splicing in lymphoblasts of affected family members. Systematic sequence analysis in two POAG patient groups (195 US and 977 German) and their respective controls (85 and 376) lead to the identification of 26 amino acid changes in 70 patients (70 of 1172; 6.0%) compared with 9 in 13 controls (13 of 461; 2.8%; P = 0.008). Molecular modeling suggests that these missense variants change ASB10 net charge or destabilize ankyrin repeats. ASB10 mRNA and protein were found to be strongly expressed in trabecular meshwork, retinal ganglion cells and ciliary body. Silencing of ASB10 transcripts in perfused anterior segment organ culture reduced outflow facility by ∼50% compared with control-infected anterior segments (P = 0.02). In conclusion, genetic and molecular analyses provide evidence for ASB10 as a glaucoma-causing gene.
Incorporating Copying Mechanism in Sequence-to-Sequence Learning (2016)

We address an important problem in sequence-to-sequence (Seq2Seq) learning referred to as copying, in which certain segments in the input sequence are selectively replicated in the output sequence. A similar phenomenon is observable in human language communication. For example, humans tend to repeat entity names or even long phrases in conversation. The challenge with regard to copying in Seq2Seq is that new machinery is needed to decide when to perform the operation. In this paper, we incorporate copying into neural network-based Seq2Seq learning and propose a new model called CopyNet with encoder-decoder structure. CopyNet can nicely integrate the regular way of word generation in the decoder with the new copying mechanism which can choose sub-sequences in the input sequence and put them at proper places in the output sequence. Our empirical study on both synthetic data sets and real world data sets demonstrates the efficacy of CopyNet. For example, CopyNet can outperform regular RNN-based model with remarkable margins on text summarization tasks.
Network Security Bible (2005)

The comprehensive A-to-Z guide on network security, fully revised and updated Network security is constantly evolving, and this comprehensive guide has been thoroughly updated to cover the newest developments. If you are responsible for network security, this is the reference you need at your side. Covering new techniques, technology, and methods for approaching security, it also examines new trends and best practices being used by many organizations. The revised Network Security Bible complements the Cisco Academy course instruction in networking security. Covers all core areas of network security and how they interrelate Fully revised to address new techniques, technology, and methods for securing an enterprise worldwide Examines new trends and best practices in use by organizations to secure their enterprises Features additional chapters on areas related to data protection/correlation and forensics Includes cutting-edge topics such as integrated cybersecurity and sections on Security Landscape, with chapters on validating security, data protection, forensics, and attacks and threats If you need to get up to date or stay current on network security, Network Security Bible, 2nd Edition covers everything you need to know.
A novel synthetic mammalian promoter derived from an internal ribosome entry site (2006)

Introduction of specific mutations into a synthetic internal ribosome entry site (IRES(GTX)) derived from the GTX homeodomain protein revealed additional transcriptional activity. This novel synthetic P(GTX) promoter exhibited consensus core promoter modules such as the initiator (Inr) and the partial downstream promoter elements (DPE) and mediated high-level expression of a variety of transgenes including the human vascular endothelial growth factor 121 (VEGF(121)), the human placental secreted alkaline phosphatase (SEAP), and the Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY) in Chinese hamster ovary cells (CHO-K1) and a variety of other mammalian and human cell lines. The spacing between Inr and DPE modules was found to be critical for promoter performance since introduction of a single nucleotide (resulting in P(GTX2)) doubled the SEAP expression levels in CHO-K1. P(GTX2) reached near 70% of P(SV40)-driven expression levels and outperformed constitutive phosphoglycerate kinase (P(PGK)) and human ubiquitin C (P(hUBC)) promoters in CHO-K1. Also, P(GTX2) was successfully engineered for macrolide-inducible transgene expression. Owing to its size of only 182 bp, P(GTX2) is one of the smallest eukaryotic promoters. Although P(GTX2) was found to be a potent promoter, it retained its IRES(GTX)-specific translation-initiation capacity. Synthetic DNAs, which combine multiple activities in a most compact sequence format may foster advances in therapeutic engineering of mammalian cells.
Discovery of a Novel Human Picornavirus in a Stool Sample from a Pediatric Patient Presenting with Fever of Unknown Origin (2007)

Fever of unknown origin (FUO) is a serious problem in the United States. An unidentified agent was cultured from the stool of an infant who presented with FUO. This virus showed growth in HFDK cells and suckling mice. Using DNase sequence-independent single-primer amplification, we identified several nucleotide sequences with a high homology to Theiler's murine encephalomyelitis virus. Nearly full-length viral genome sequencing and phylogenetic analysis demonstrate that this virus is a member of the Cardiovirus genus of the Picornaviridae family.
Detection of gastric slow wave propagation from the cutaneous electrogastrogram (1999)

The gastric slow wave is originated in the proximal stomach and propagates distally toward the pylorus. It determines the maximum frequency and propagation of gastric contractions. The aim of this study was to detect the propagation of the gastric slow wave from the surface electrogastrogram (EGG). The study was performed in 11 healthy subjects of normal weight. Gastric myoelectrical activity was recorded for 1 h in the fasting state with the use of a specially designed multichannel recording device that was composed of four identical amplifiers with cutoff frequencies of 1.8 and 16.0 cycles/min. Four active electrodes were placed on the abdomen along the gastric axis and were connected to a common reference electrode placed near the xiphoid process, yielding four-channel bipolar EGG signals. Cross-covariance analysis was performed to compute the time lag among the four channels. There was a time lag in EGG waveform between channels 1 and 4 (9.6 +/- 1.1 s); the average time during which the time lag was observed (>/=3 s) was 89.9 +/- 9.0%. There was a significant difference in the time lag among different adjacent channels (P < 0.04); the time lag observed between channels 3 and 4 was significantly smaller than that between channels 1 and 2 (P < 0.03). No correlation was found between the body mass index and the time lag between channels 1 and 4 (r = -0.31, P = 0.3). It was concluded that, with a multichannel recording device with identical multiamplifiers and an appropriate arrangement of abdominal electrodes, the propagation of the gastric slow wave could be identified from the EGG in healthy subjects. This method may be used to detect the coupling of the gastric slow wave noninvasively.
Outcome of Severe Refractory Status Epilepticus in Children (2001)

Our data demonstrate a high mortality and morbidity for childhood RSE. Mortality is related to etiology and is higher in younger children and with multifocal or generalized abnormalities on the initial EEG.
Heme Oxygenase-1 Induction Does Not Improve Vascular Relaxation in Angiotensin II Hypertensive Mice (2008)

These results suggest that induction of HO-1 lowers Ang II-dependent hypertension through a mechanism independent of improved vascular relaxation.
Aspirin and Nonsteroidal Anti-inflammatory Drug Use and the Risk of Subsequent Colorectal Cancer (1994)

The results of previous experimental animal models, interventional case studies, and some but not all epidemiological investigations and the present data point toward a causal relationship between NSAID use and the prevention of cancer of the large bowel and rectum. Because of the potential gastrointestinal and renal side effects of NSAID use, particularly in the elderly, chemoprevention trials are now needed to allow risk-benefit analysis in populations at high risk for colorectal cancer.
An in situ-forming zwitterionic hydrogel as vitreous substitute (2014)

Zwitterionic polymers have shown ultra-low biofouling properties at surfaces and excellent biocompatibility as implant. In this study, an in situ-forming zwitterionic hydrogel was designed and evaluated, both in vitro and in vivo, as a long-term vitreous substitute. The zwitterionic polymer poly(MPDSA-co-AC) was designed as a copolymer of the sulfobetaine methacrylamide and acryloyl cystamine monomers, providing the zwitterionic components and the thiol functional groups, respectively. The in situ gelation was via the thiol-ene Michael addition reaction with α-PEG-MA as the crosslinker. The gelation time, rheological properties, swelling profiles, and the transparency of zwitterionic hydrogels were studied in detail. Two systems with different crosslinker concentrations were tested in a rabbit model, and the one with the thiol-ene ratio of 2 : 1 showed excellent biocompatibility in vivo, formed space-filling hydrogels and remained transparent in the vitreous cavity for the 2 month implantation period. Therefore, in situ-forming zwitterionic hydrogels represent a promising material system as a vitreous substitute and possibly for other soft tissue replacements.
SmartWater Synergy with Surfactant Chemicals: An Electro-Kinetic Study (2019)

Abstract SmartWater flooding through the injection of optimized chemistry water has lately become an attractive proposition for enhanced oil recovery in carbonate reservoirs. The wettability alteration towards water-wet conditions caused by favorable surface charge alteration is identified as the main mechanism responsible for oil recovery. In this experimental investigation, the impact of SmartWater/surfactant synergy on wettability alteration was thoroughly studied by measuring zeta-potentials at calcite/brine and crude oil/brine interfaces using electrophoresis technique. Different types of surfactants are considered including: anionic, amphoteric and non-ionic. Four different water recipes representing SmartWater (10-times reduced salinity) were chosen at a fixed lower salinity as well as the high salinity water (HSW). The results showed that both anionic surfactants increased the magnitude of the negative zeta-potentials at the interfaces by almost same order of magnitude. The negative zeta-potentials of calcite and crude oil were increased the most with anionic surfactants in NaCl brine. SmartWater showed relatively higher negative zeta-potentials for calcite when compared to Na2SO4 brine and HSW in the presence of anionic surfactant. These results indicate that both NaCl brine and SmartWater can synergistically combine with anionic surfactants for effective wettability alteration in carbonates. Amphoteric surfactant showed a negligible impact on electrical double layer (EDL) expansion and consequently the wettability alteration. The nonionic surfactant induced electrostatic repulsion forces at both calcite/brine and crude oil/brine interfaces in high salinity seawater and as a result it can be considered as the best chemical formulation to reduce interfacial tension and cause wettability alteration in conventional chemical flooding processes. The negligible impact of adding surfactant chemicals on the measured di-electric constant of different brines confirmed the robustness of zeta-potential values reported in this study. This work for the first time evaluated the synergistic effects of different brines including the SmartWater with surfactant chemicals by measuring zeta-potentials at calcite/brine and oil/brine interfaces. The optimally suited water recipes were identified to synergistically combine with these chemicals to enhance wettability alteration in carbonates. The new knowledge gained from this electro-kientic study will provide practical guidance on how to design efficient chemical flooding processes for enhanced oil recovery in carbonate reservoirs.
High-Throughput Sequencing of the Zebrafish Antibody Repertoire (2009)

Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.
Constraints methods for flexible models (1988)

Simulating flexible models can create aesthetic motion for computer animation. Animators can control these motions through the use of constraints on the physical behavior of the models. This paper shows how to use mathematical constraint methods based on physics and on optimization theory to create controlled, realistic animation of physically-based flexible models. Two types of constraints are presented in this paper: reaction constraints (RCs) and augrmented Lagrangian constraints (ALCs). RCs allow the fast computation of collisions of flexible models with polygonal models. In addition, RCs allow flexible models to be pushed and pulled under the control of an animator. ALCs create animation effects such as volume-preserving squashing and the molding of taffy-like substances. ALCs are compatible with RCs. In this paper, we describe how to apply these constraint methods to a flexible model that uses finite elements.
Anti-B cell antibodies for the treatment of monoclonal Epstein-Barr virus-induced lymphoproliferative syndrome after multivisceral transplantation. (1994)

Epstein-Barr virus-induced lymphoproliferative syndrome (EBV-LPS) is associated with OKT3 therapy in transplant patients. Response to chemotherapy or radiation is generally poor, while polyclonal EBV-LPS has had favorable responses to therapy with CD21 and CD24 monoclonal antibodies. Oligoclonal disease has not been previously reported to respond to therapy with CD21 and CD24. We report a 27-y old woman who developed a monoclonal EBV-LPS (confirmed by southern analysis of tumour for EBV DNA) after 180 mg of OKT3 for a multivisceral transplant. The patient achieved clinical remission for more than 2 months, but later died from cytomegalovirus pneumonia. Levels of CD21 and CD24 were > 2000 ng/ml during therapy and no human anti-mouse antibodies were formed. Peripheral blood B cells were cleared during therapy. We conclude that CD21 and CD24 monoclonal antibodies may be of value in the therapy of oigoclonal EBV-LPS, and merit further study.
The 4.1-like proteins of the bovine lens: spectrin-binding proteins closely related in structure to red blood cell protein 4.1. (1986)

The superficial cortical fiber cells of the bovine lens contain membrane-associated proteins of 150,000, 80,000, and 78,000 D that cross-react with antisera prepared against red blood cell (RBC) protein 4.1 (Aster, J. C., G. J. Brewer, S. M. Hanash, and H. Maisel, 1984, Biochem. J., 224:609-616). To further study their relationship to protein 4.1, these proteins were immunoprecipitated from detergent extracts of crude lens membranes with purified polyclonal and monoclonal anti-4.1 antibodies and resolved by SDS PAGE. The electrophoretic mobilities of the lens proteins of 80,000 and 78,000 D were found to be identical to bovine RBC protein 4.1a and protein 4.1b, respectively. One- and two-dimensional peptide mapping revealed that a high degree of structural homology exists among all three of the lens 4.1-like proteins and RBC protein 4.1a and protein 4.1b. Despite the large difference in apparent molecular mass, the 150,000-D lens protein showed only minor peptide map differences. A nitrocellulose filter overlay assay showed that all three of the lens 4.1-like proteins bind to RBC and lens spectrins. We conclude that the bovine lens contains proteins of 80,000 and 78,000 D that are highly similar to protein 4.1 in structure and functional capacity. Additionally, the lens also contains a 4.1 isomorph of 150 kD. Analogous to RBC protein 4.1, these proteins may function in the lens by promoting association of spectrin with actin and by playing a role in the coupling of lens cytoskeleton to plasma membrane.
A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification (2007)

Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MLL. Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79-specific methylase activity, displayed a robust RNAPolII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole-riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene-specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation.
Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. (1998)

To determine whether multidrug resistance (MDR1) P-glycoprotein (Pgp) expression correlated with clinical MDR1-related drug resistance, we established a protocol for quantitative measurement of Pgp expression and in vitro drug resistance in doxorubicin resistant MCF7 breast cancer cell lines and 359 freshly resected specimens of breast carcinoma. Pgp expression was detected with 4E3, UIC2, and JSB-1 monoclonal antibodies using flow cytometry and immunohistochemistry (IHC). Pgp function was determined using PSC833 in a drug resistance-reversal assay and with a three-dimensional agarose-based extreme drug resistance assay. MCF7 calibrator cell lines expressed Pgp, which was functional and in proportion to the degree of drug resistance. Flow cytometry, UIC2 shift assays, IHC scores, and determination of absorbance products by image analysis were all highly correlated (r > 0.9). Overall Pgp expression increased from 11% in untreated patients to 30% in patients who had previously received chemotherapy. Compared with Pgp-negative tumors, a significant increase in doxorubicin and Taxol resistance was seen for breast cancers that expressed Pgp, regardless of prior treatment. A strong correlation between the degree of Pgp expression and in vitro resistance to Taxol and doxorubicin (but not to 5-fluorouracil) was found when either IHC scores or image analysis-based methods were used to quantify Pgp expression (n = 185, P < 0.0001). The degree of Pgp expression strongly correlated with the degree of drug resistance in the clinical specimens studied. These data suggest that (a) Pgp contributes to clinical MDR1-related drug resistance, and (b) both intrinsic and acquired expression of Pgp in breast cancer may contribute in part to therapeutic failure and relapse.